package protobuf.opencb

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* Variant origin. `SO_0001781`: de novo variant. http://purl.obolibrary.org/obo/SO_0001781 `SO_0001778`: germline variant. http://purl.obolibrary.org/obo/SO_0001778 `SO_0001775`: maternal variant. http://purl.obolibrary.org/obo/SO_0001775 `SO_0001776`: paternal variant. http://purl.obolibrary.org/obo/SO_0001776 `SO_0001779`: pedigree specific variant. http://purl.obolibrary.org/obo/SO_0001779 `SO_0001780`: population specific variant. http://purl.obolibrary.org/obo/SO_0001780 `SO_0001777`: somatic variant. http://purl.obolibrary.org/obo/SO_0001777

Used in: EvidenceEntry

• de_novo_variant = 0

• germline_variant = 1

• maternal_variant = 2

• paternal_variant = 3

• pedigree_specific_variant = 4

• population_specific_variant = 5

• somatic_variant = 6

Used in: StudyEntry, VcfRecord

• string chromosome = 1

• int32 start = 2

• int32 end = 3

• string reference = 4

  * Reference allele.

• string alternate = 5

  * Alternate allele.

• VariantType type = 6

  * Type of variation: single nucleotide, indel or structural variation.

• map<string, string> query = 3

• map<string, string> options = 4

Used in: StructuralVariation

• optional BreakendMate mate = 1

• BreakendOrientation orientation = 2

• string insSeq = 3

Used in: Breakend

• string chromosome = 1

• int32 position = 2

• int32 ciPositionLeft = 3

• int32 ciPositionRight = 4

SE | (Start -> End) | s | t[p[ | piece extending to the right of p is joined after t SS | (Start -> Start) | s | t]p] | reverse comp piece extending left of p is joined after t ES | (End -> Start) | s | ]p]t | piece extending to the left of p is joined before t EE | (End -> End) | s | [p[t | reverse comp piece extending right of p is joined before t

Used in: Breakend

• SE = 0

• SS = 1

• ES = 2

• EE = 3

Used in: CancerHotspotVariantAnnotation

• string aminoacidAlternate = 1

• int32 count = 2

• map<string, int32> sampleCount = 3

Used in: VariantAnnotation

• string geneName = 1

• string proteinId = 2

• int32 aminoacidPosition = 3

• string aminoacidReference = 4

• string cancerType = 5

• map<string, double> scores = 6

• map<string, int32> cancerTypeCount = 7

• map<string, int32> organCount = 8

• repeated CancerHotspotAlternateAnnotation variants = 9

• string source = 10

* Mendelian variants classification with ACMG terminology as defined in Richards, S. et al. (2015). Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405–423. https://doi.org/10.1038/gim.2015.30. Classification for pharmacogenomic variants, variants associated to disease and somatic variants based on the ACMG recommendations and ClinVar classification (https://www.ncbi.nlm.nih.gov/clinvar/docs/clinsig/). `benign_variant` : Benign variants interpreted for Mendelian disorders `likely_benign_variant` : Likely benign variants interpreted for Mendelian disorders with a certainty of at least 90% `pathogenic_variant` : Pathogenic variants interpreted for Mendelian disorders `likely_pathogenic_variant` : Likely pathogenic variants interpreted for Mendelian disorders with a certainty of at least 90% `uncertain_significance` : Uncertain significance variants interpreted for Mendelian disorders. Variants with conflicting evidences should be classified as uncertain_significance

Used in: VariantClassification

• benign = 0

• likely_benign = 1

• VUS = 2

• likely_pathogenic = 3

• pathogenic = 4

• uncertain_significance = 5

* Confidence based on the Confidence Information Ontology `CIO_0000029`: high confidence level http://purl.obolibrary.org/obo/CIO_0000029 `CIO_0000031`: low confidence level http://purl.obolibrary.org/obo/CIO_0000031 `CIO_0000030`: medium confidence level http://purl.obolibrary.org/obo/CIO_0000030 `CIO_0000039`: rejected http://purl.obolibrary.org/obo/CIO_0000039

Used in: EvidenceEntry

• low_confidence_level = 0

  CIO_0000031

• medium_confidence_level = 1

  CIO_0000030

• high_confidence_level = 2

  CIO_0000029

• rejected = 3

  CIO_0000039

Used in: VariantAnnotation

• string gene_name = 1

• string ensembl_gene_id = 2

• string ensembl_transcript_id = 3

• string strand = 4

• string biotype = 5

• repeated ExonOverlap exon_overlap = 6

• int32 cdna_position = 8

• int32 cds_position = 9

• string codon = 10

• optional ProteinVariantAnnotation protein_variant_annotation = 11

• repeated SequenceOntologyTerm sequence_ontology_terms = 12

• string gene_id = 13

• string transcript_id = 14

• repeated string hgvs = 15

• repeated SpliceScores spliceScores = 16

• repeated string transcriptFlags = 17

• string source = 18

• repeated string acmg = 19

* The consistency of evidences for a given phenotype. This aggregates all evidences for a given phenotype and all evidences with no phenotype associated (e.g.: in silico impact prediction, population frequency). This is based on the Confidence Information Ontology terms. `CIO_0000033`: congruent, all evidences are consistent. http://purl.obolibrary.org/obo/CIO_0000033 `CIO_0000034`: conflict, there are conflicting evidences. This should correspond to a `VariantClassification` of `uncertain_significance` for mendelian disorders. http://purl.obolibrary.org/obo/CIO_0000034 `CIO_0000035`: strongly conflicting. http://purl.obolibrary.org/obo/CIO_0000035 `CIO_0000036`: weakly conflicting. http://purl.obolibrary.org/obo/CIO_0000036

Used in: EvidenceEntry

• congruent = 0

  CIO_0000033

• conflict = 1

  CIO_0000034

• weakly_conflicting = 2

  CIO_0000035

• strongly_conflicting = 3

  CIO_0000036

Used in: VariantAnnotation

• string source = 1

• string method = 2

• string name = 3

• double value = 4

Used in: VariantAnnotation

• string chromosome = 1

• string stain = 2

• string name = 3

• int32 start = 4

• int32 end = 5

Used in: VariantAnnotation

• string therapeuticContext = 1

• string pathway = 2

• string effect = 3

• string association = 4

• string status = 5

• string evidence = 6

• repeated string bibliography = 7

* Pharmacogenomics drug response variant classification `responsive` : A variant that confers response to a treatment `resistant` : A variant that confers resistance to a treatment `toxicity` : A variant that is associated with drug-induced toxicity `indication` : A variant that is required in order for a particular drug to be prescribed `contraindication` : A variant that if present, a particular drug should not be prescribed `dosing` : A variant that results in an alteration in dosing of a particular drug in order to achieve INR, reduce toxicity or increase efficacy `increased_monitoring` : increase vigilance or increased dosage monitoring may be required for a patient with this variant to look for signs of adverse drug reactions `efficacy` : a variant that affects the efficacy of the treatment

Used in: VariantClassification

• responsive = 0

  DEPRECATED: kept just for retrocompatibility purposes

• altered_sensitivity = 1

• reduced_sensitivity = 2

• increased_sensitivity = 3

• altered_resistance = 4

• increased_resistance = 5

• reduced_resistance = 6

• increased_risk_of_toxicity = 7

• reduced_risk_of_toxicity = 8

• altered_toxicity = 9

• adverse_drug_reaction = 10

• indication = 11

• contraindication = 12

• dosing_alteration = 13

• increased_dose = 14

• reduced_dose = 15

• increased_monitoring = 16

• increased_efficacy = 17

• reduced_efficacy = 18

• altered_efficacy = 19

* This is the list of ethnics in ONS16 `D`: Mixed: White and Black Caribbean `E`: Mixed: White and Black African `F`: Mixed: White and Asian `G`: Mixed: Any other mixed background `A`: White: British `B`: White: Irish `C`: White: Any other White background `L`: Asian or Asian British: Any other Asian background `M`: Black or Black British: Caribbean `N`: Black or Black British: African `H`: Asian or Asian British: Indian `J`: Asian or Asian British: Pakistani `K`: Asian or Asian British: Bangladeshi `P`: Black or Black British: Any other Black background `S`: Other Ethnic Groups: Any other ethnic group `R`: Other Ethnic Groups: Chinese `Z`: Not stated

Used in: EvidenceEntry

• D = 0

• E = 1

• F = 2

• G = 3

• A = 4

• B = 5

• C = 6

• L = 7

• M = 8

• N = 9

• H = 10

• J = 11

• K = 12

• P = 13

• S = 14

• R = 15

• Z = 16

* An entry for an evidence

Used in: VariantAnnotation

• optional EvidenceSource source = 1

  * Source of the evidence

• repeated EvidenceSubmission submissions = 2

  * The list of submissions

• optional SomaticInformation somaticInformation = 3

  * The somatic information

• string url = 4

  * URL of source if any

• string id = 5

  * ID of record in the source

• string assembly = 6

  * The reference genome assembly

• repeated AlleleOrigin alleleOrigin = 7

  * List of allele origins

• repeated HeritableTrait heritableTraits = 8

  * Heritable traits associated to this evidence

• repeated GenomicFeature genomicFeatures = 9

  * The transcript to which the evidence refers

• optional VariantClassification variantClassification = 10

  * The variant classification

• EvidenceImpact impact = 11

  * Impact of evidence. Should be coherent with the classification of impact if provided.

• Confidence confidence = 12

  * The curation confidence.

• ConsistencyStatus consistencyStatus = 13

  * The consistency status. This is applicable to complex evidences (e.g.: ClinVar)

• EthnicCategory ethnicity = 14

  * Ethnicity

• Penetrance penetrance = 15

  * The penetrance of the phenotype for this genotype. Value in the range [0, 1]

• bool variableExpressivity = 16

  * Variable expressivity of a given phenotype for the same genotype

• string description = 17

  * Evidence description

• repeated Property additionalProperties = 18

  * A list of additional properties in the form name-value.

• repeated string bibliography = 19

  * Bibliography

* Evidence of pathogenicity and benign impact as defined in Richards, S. et al. (2015). Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405–423. https://doi.org/10.1038/gim.2015.30 Evidence of pathogenicity: `very_strong`: - PVS1 null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease `strong`: - PS1 Same amino acid change as a previously established pathogenic variant regardless of nucleotide change - PS2 De novo (both maternity and paternity confirmed) in a patient with the disease and no family history - PS3 Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product - PS4 The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls `moderate`: - PM1 Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation - PM2 Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium - PM3 For recessive disorders, detected in trans with a pathogenic variant - PM4 Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants - PM5 Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before - PM6 Assumed de novo, but without confirmation of paternity and maternity `supporting`: - PP1 Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease - PP2 Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease - PP3 Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.) - PP4 Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology - PP5 Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation Evidence of benign impact: `stand_alone`: - BA1 Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium `strong`: - BS1 Allele frequency is greater than expected for disorder - BS2 Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age - BS3 Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing - BS4 Lack of segregation in affected members of a family `supporting`: - BP1 Missense variant in a gene for which primarily truncating variants are known to cause disease - BP2 Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern - BP3 In-frame deletions/insertions in a repetitive region without a known function - BP4 Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.) - BP5 Variant found in a case with an alternate molecular basis for disease - BP6 Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation - BP7 A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved

Used in: EvidenceEntry

• very_strong = 0

• strong = 1

• moderate = 2

• supporting = 3

• stand_alone = 4

* The source of an evidence.

Used in: EvidenceEntry

• string name = 1

  * Name of source

• string version = 2

  * Version of source

• string date = 3

  * The source date.

* The submission information

Used in: EvidenceEntry

• string submitter = 1

  * The submitter

• string date = 2

  * The submission date

• string id = 3

  * The submission id

Used in: Transcript

• string id = 1

• string chromosome = 2

• int32 start = 3

• int32 end = 4

• string strand = 5

• int32 genomic_coding_start = 6

• int32 genomic_coding_end = 7

• int32 cdna_coding_start = 8

• int32 cdna_coding_end = 9

• int32 cds_start = 10

• int32 cds_end = 11

• int32 phase = 12

• int32 exon_number = 13

• string sequence = 14

Used in: ConsequenceType

• string number = 1

• float percentage = 2

Used in: GeneAnnotation, VariantAnnotation

• string gene_name = 1

• string transcript_id = 2

• string experimental_factor = 3

• string factor_value = 4

• string experiment_id = 5

• string technology_platform = 6

• ExpressionCall expression = 7

• float pvalue = 8

Used in: Expression

• DOWN = 0

• UP = 1

* The feature types

Used in: GenomicFeature

• regulatory_region = 0

• gene = 1

• transcript = 2

• protein = 3

Used in: VcfSlice

• repeated string info_keys = 1

• repeated uint32 default_info_keys = 2

• repeated string filters = 3

  Possible filter compositions. Delimited by ';' Where the first filter is the default one

• repeated string formats = 5

  Possible formats compositions. Delimited by ':' Where the first format is the default one

• repeated string gts = 6

  Possible genotypes seen on the slice. Where the first GT is the default one

Used in: StudyEntry

• string fileId = 1

• optional OriginalCall call = 2

• map<string, string> data = 3

• string id = 1

• string name = 2

• string chromosome = 3

• int32 start = 4

• int32 end = 5

• string biotype = 6

• string status = 7

• string strand = 8

• string source = 9

• string description = 10

• repeated Transcript transcripts = 11

• optional MiRNAGene mirna = 12

• optional GeneAnnotation annotation = 13

Used in: Gene

• repeated Expression expression = 1

• repeated GeneDrugInteraction drugInteractions = 2

• repeated GeneTraitAssociation geneTraitAssociation = 3

Used in: VariantAnnotation

• string id = 1

• string source = 2

• string tier = 3

• bool somatic = 4

• bool germline = 5

• repeated string somaticTumourTypes = 6

• repeated string germlineTumourTypes = 7

• repeated string syndromes = 8

• repeated string tissues = 9

• repeated string modeOfInheritance = 10

• repeated string roleInCancer = 11

• repeated string mutationTypes = 12

• repeated string translocationPartners = 13

Used in: GeneAnnotation, VariantAnnotation

• string gene_name = 1

• string drug_name = 2

• string source = 3

• string study_type = 4

• string type = 5

• string interaction_type = 6

• string chembl_id = 7

• repeated string publications = 8

Used in: GeneFusionSummary

• string geneName = 1

• string chromosome = 2

• int32 position = 3

• string strand = 4

Used in: VariantAnnotation

• string pair = 1

• string source = 2

• optional GeneFusionBreakpoint headGene = 3

• optional GeneFusionBreakpoint tailGene = 4

• repeated string pmid = 5

• repeated string diseases = 6

• bool kinase = 7

• bool oncogene = 8

• bool tumorSuppresor = 9

• bool receptor = 10

• bool transcriptionFactor = 11

Used in: VariantAnnotation

• string geneName = 1

• string status = 2

• string expressedAllele = 3

• string source = 4

• map<string, string> attributes = 5

Used in: VariantAnnotation

• string id = 1

• string name = 2

• string biotype = 3

Used in: GeneAnnotation, VariantAnnotation

• string id = 1

• string name = 2

• string hpo = 3

• float score = 4

• int32 numberOfPubmeds = 5

• repeated string associationTypes = 6

• repeated string sources = 7

• string source = 8

* The genomic feature

Used in: EvidenceEntry

• FeatureTypes featureType = 1

  * Feature Type

• string ensemblId = 2

  * Feature used, this should be a feature ID from Ensembl, (i.e, ENST00000544455)

• map<string, string> xrefs = 3

  * Others IDs. Fields like the HGNC symbol if available should be added here

Used in: VariantAnnotation

• int32 start = 1

• int32 end = 2

• string sequence = 3

• optional Response response = 1

• map<string, string> values = 2

Used in: VariantAnnotation

• string source = 1

• string region = 2

• string snpId = 3

• string riskAllele = 4

• double riskAlleleFrequency = 5

• repeated GwasAssociationStudy studies = 6

Used in: GwasAssociation

• string pubmedid = 1

• string study = 2

• string studyAccession = 3

• string initialSampleSizeDescription = 4

• int32 initialSampleSize = 5

• string platform = 6

• string genotypingTechnology = 7

• repeated GwasAssociationStudyTrait traits = 8

Used in: GwasAssociationStudy

• string diseaseTrait = 1

• repeated string strongestSnpRiskAllele = 2

• repeated OntologyTermAnnotation ontologies = 3

• repeated GwasAssociationStudyTraitScores scores = 4

Used in: GwasAssociationStudyTrait

• double pValue = 1

• double pValueMlog = 2

• string pValueText = 3

• double orBeta = 4

• string percentCI = 5

* The entity representing a phenotype and its inheritance pattern.

Used in: EvidenceEntry

• string trait = 1

  * The trait (e.g.: HPO term, MIM term, DO term etc.)

• ModeOfInheritance inheritanceMode = 2

  * The mode of inheritance

Used in: StudyEntry

• IssueEntry.IssueType type = 1

• optional SampleEntry sample = 2

• map<string, string> data = 3

Used in: IssueEntry

• DUPLICATION = 0

• DISCREPANCY = 1

• MENDELIAN_ERROR = 2

• DE_NOVO = 3

• COMPOUND_HETEROZYGOUS = 4

• optional Response response = 1

• int64 value = 2

• optional Response response = 1

• map<string, string> values = 2

Used in: Gene

• string miRBase_accession = 1

• string miRBase_id = 2

• string status = 3

• string sequence = 4

• repeated string alias = 5

• repeated MiRNAGene.MiRNAMature matures = 6

Used in: MiRNAGene

• string miRBase_accession = 1

• string miRBase_id = 2

• string sequence = 3

• int32 cdna_start = 4

• int32 cdna_end = 5

* An enumeration for the different mode of inheritances: `monoallelic_not_imprinted`: MONOALLELIC, autosomal or pseudoautosomal, not imprinted `monoallelic_maternally_imprinted`: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) `monoallelic_paternally_imprinted`: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) `monoallelic`: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown `biallelic`: BIALLELIC, autosomal or pseudoautosomal `monoallelic_and_biallelic`: BOTH monoallelic and biallelic, autosomal or pseudoautosomal `monoallelic_and_more_severe_biallelic`: BOTH monoallelic and biallelic, autosomal or pseudoautosomal (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal `xlinked_biallelic`: X-LINKED: hemizygous mutation in males, biallelic mutations in females `xlinked_monoallelic`: X linked: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) `mitochondrial`: MITOCHONDRIAL `unknown`: Unknown `NA`: Not applicable

Used in: HeritableTrait

• monoallelic = 0

• monoallelic_not_imprinted = 1

• monoallelic_maternally_imprinted = 2

• monoallelic_paternally_imprinted = 3

• biallelic = 4

• monoallelic_and_biallelic = 5

• monoallelic_and_more_severe_biallelic = 6

• xlinked_biallelic = 7

• xlinked_monoallelic = 8

• mitochondrial = 9

• unknown = 10

• NA = 11

Used in: GwasAssociationStudyTrait, PolygenicScoreAnnotation

• string id = 1

• string name = 2

• string description = 3

• string source = 4

• string url = 5

• map<string, string> attributes = 6

Used in: FileEntry

• string variantId = 1

  * Original variant ID before normalization including all secondary alternates.

• int32 alleleIndex = 2

  * Alternate allele index of the original multi-allellic variant call in which was decomposed.

* Penetrance assumed in the analysis

Used in: EvidenceEntry

• complete = 0

• incomplete = 1

Used in: VariantAnnotation

• string id = 1

• string name = 2

• string source = 3

• repeated string types = 4

• string smiles = 5

• string inChI = 6

• repeated PharmacogenomicsClinicalAnnotation annotations = 7

Used in: PharmacogenomicsClinicalAnnotation

• string allele = 1

• string annotation = 2

• string description = 3

Used in: Pharmacogenomics

• string variantId = 1

• repeated string geneNames = 2

• repeated string phenotypes = 3

• repeated string phenotypeTypes = 4

• string confidence = 5

• string score = 6

• string url = 7

• string summary = 8

• repeated string pubmed = 9

• repeated PharmacogenomicsAlleles alleles = 10

Used in: VariantAnnotation

• string id = 1

• string name = 2

• string source = 3

• string version = 4

• repeated OntologyTermAnnotation traits = 5

• repeated PubmedReference pubmedReferences = 6

• repeated StringMap values = 7

• repeated PolygenicScoreVariant variants = 8

Used in: PolygenicScoreAnnotation

• string effectAllele = 1

• string otherAllele = 2

• map<string, string> values = 3

Used in: VariantAnnotation

• string study = 1

• string population = 2

• string ref_allele = 3

• string alt_allele = 4

• float ref_allele_freq = 5

• float alt_allele_freq = 6

• float ref_hom_genotype_freq = 7

• float het_genotype_freq = 8

• float alt_hom_genotype_freq = 9

• int32 ref_allele_count = 10

• int32 alt_allele_count = 11

• int32 ref_hom_genotype_count = 12

• int32 het_genotype_count = 13

• int32 alt_hom_genotype_count = 14

* A property in the form of name-value pair. Names are restricted to ontology ids, they should be checked against existing ontologies in resources like Ontology Lookup Service.

Used in: EvidenceEntry

• string id = 1

  * The ontology term id or accession in OBO format ${ONTOLOGY_ID}:${TERM_ID} (http://www.obofoundry.org/id-policy.html)

• string name = 2

  * The ontology term name

• string value = 3

  * Optional value for the ontology term, the type of the value is not checked (i.e.: we could set the pvalue term to "significant" or to "0.0001")

Used in: ProteinVariantAnnotation

• string id = 1

• int32 start = 2

• int32 end = 3

• string type = 4

• string description = 5

Used in: ConsequenceType

• string uniprot_accession = 1

• string uniprot_name = 2

• int32 position = 3

• string proteinId = 4

  Ensembl or RefSeq protein ID

• string reference = 5

• string alternate = 6

• string uniprot_variant_id = 7

• string functional_description = 8

• repeated Score substitution_scores = 9

• repeated string keywords = 10

• repeated ProteinFeature features = 11

Used in: PolygenicScoreAnnotation

• string id = 1

• string title = 2

• string journal = 3

• string date = 4

• string url = 5

• string id = 1

• string chromosome = 2

• string source = 3

• string feature_type = 4

• int32 start = 5

• int32 end = 6

• string score = 7

• string strand = 8

• string frame = 9

• string item_r_g_b = 10

• string name = 11

• string feature_class = 12

• string alias = 13

• repeated string cell_types = 14

• string matrix = 15

Used in: VariantAnnotation

• string id = 1

• string chromosome = 2

• int32 start = 3

• int32 end = 4

• int32 period = 5

• int32 consensusSize = 6

• float copy_number = 7

• float percentage_match = 8

• float score = 9

• string sequence = 10

• string source = 11

Used in: GroupResponse, LongResponse, MapResponse, StringArrayResponse, StringResponse

• string id = 1

• string warning = 2

• string error = 3

Used in: IssueEntry, StudyEntry

• string sampleId = 1

• int32 fileIndex = 2

• repeated string data = 3

Used in: ProteinVariantAnnotation, VariantAnnotation

• double score = 1

• string source = 2

• string description = 3

Used in: ConsequenceType

• string accession = 1

• string name = 2

* The somatic information.

Used in: EvidenceEntry

• string primarySite = 1

  * The primary site

• string siteSubtype = 2

  * The primary site subtype

• string primaryHistology = 3

  * The primary histology

• string histologySubtype = 4

  * The histology subtype

• string tumourOrigin = 5

  * The tumour origin

• string sampleSource = 6

  * The sample source, e.g. blood-bone marrow, cell-line, pancreatic

Used in: ConsequenceType

• string source = 1

• map<string, double> scores = 2

• optional Response response = 1

• repeated string values = 2

Used in: PolygenicScoreAnnotation

• map<string, string> values = 1

• optional Response response = 1

• string value = 2

Used in: Variant

• int32 ciStartLeft = 1

• int32 ciStartRight = 2

• int32 ciEndLeft = 3

• int32 ciEndRight = 4

• int32 copyNumber = 5

  * Number of copies for CNV variants.

• string leftSvInsSeq = 6

  * Inserted sequence for long INS

• string rightSvInsSeq = 7

• StructuralVariation.StructuralVariantType type = 8

  * Structural variation type: COPY_NUMBER_GAIN, COPY_NUMBER_LOSS, TANDEM_DUPLICATION, ...

• optional Breakend breakend = 9

* Type of structural variation <ul> <li>COPY_NUMBER_GAIN for CNVs</li> <li>COPY_NUMBER_LOSS for CNVs</li> <li>TANDEM_DUPLICATION for DUP</li> </ul>

Used in: StructuralVariation

• COPY_NUMBER_GAIN = 0

  unused = 0; // SO:0001742

  SO:0001742

• COPY_NUMBER_LOSS = 1

  SO:0001743

• TANDEM_DUPLICATION = 2

  SO:1000173

Used in: Variant

• string studyId = 1

• repeated FileEntry files = 2

• repeated AlternateCoordinate secondaryAlternates = 3

  * Alternate alleles that appear along with a variant alternate.

• repeated string sampleDataKeys = 4

• repeated SampleEntry samples = 5

• repeated VariantStats stats = 6

• repeated IssueEntry issues = 7

• repeated VariantScore scores = 8

* Association of variants to a given trait. `established_risk_allele` : Established risk allele for variants associated to disease `likely_risk_allele` : Likely risk allele for variants associated to disease `uncertain_risk_allele` : Uncertain risk allele for variants associated to disease `protective` : Protective allele

Used in: VariantClassification

• established_risk_allele = 0

• likely_risk_allele = 1

• uncertain_risk_allele = 2

• protective = 3

Used in: Gene

• string id = 1

• string name = 2

• string chromosome = 3

• int32 start = 4

• int32 end = 5

• string biotype = 6

• string status = 7

• string strand = 8

• int32 genomic_coding_start = 9

• int32 genomic_coding_end = 10

• int32 cdna_coding_start = 11

• int32 cdna_coding_end = 12

• int32 cds_length = 13

• string cdna_sequence = 14

• string protein_id = 15

• string protein_sequence = 16

• string description = 17

• repeated Xref xrefs = 18

• repeated TranscriptTfbs tfbs = 19

• repeated Exon exons = 20

• repeated string annotation_flags = 21

Used in: Transcript

• string tf_name = 1

• string pwm = 2

• string chromosome = 3

• int32 start = 4

• int32 end = 5

• string strand = 6

• int32 relative_start = 7

• int32 relative_end = 8

• float score = 9

* Variant classification according to its relation to cancer aetiology. `driver` : Driver variants `passenger` : Passenger variants `modifier` : Modifier variants

Used in: VariantClassification

• driver = 0

• passenger = 1

• modifier = 2

• string chromosome = 1

  * Chromosome where the genomic variation occurred.

• int32 start = 2

  * Normalized position where the genomic variation starts. <ul> <li>SNVs have the same start and end position</li> <li>Insertions start in the last present position: if the first nucleotide is inserted in position 6, the start is position 5</li> <li>Deletions start in the first previously present position: if the first deleted nucleotide is in position 6, the start is position 6</li> </ul>

• int32 end = 3

  * Normalized position where the genomic variation ends. <ul> <li>SNVs have the same start and end positions</li> <li>Insertions end in the first present position: if the last nucleotide is inserted in position 9, the end is position 10</li> <li>Deletions ends in the last previously present position: if the last deleted nucleotide is in position 9, the end is position 9</li> </ul>

• string reference = 4

  * Reference allele.

• string alternate = 5

  * Alternate allele.

• string strand = 6

  * Reference strand for this variant

• optional StructuralVariation sv = 14

  * Information regarding Structural Variants

• string id = 13

  * The variant ID.

• repeated string names = 7

  * Other names used for this genomic variation.

• int32 length = 8

  * Length of the genomic variation, which depends on the variation type. <ul> <li>SNVs have a length of 1 nucleotide</li> <li>Indels have the length of the largest allele</li> </ul>

• VariantType type = 9

  * Type of variation: single nucleotide, indel or structural variation.

• repeated StudyEntry studies = 11

  * Information specific to each study the variant was read from, such as samples or statistics.

• optional VariantAnnotation annotation = 12

  * Annotations of the genomic variation.

Used in: Variant

• string chromosome = 1

• int32 start = 2

• int32 end = 3

• string reference = 4

• string alternate = 5

• string ancestral_allele = 6

• string id = 7

• repeated VariantAnnotation.Xref xrefs = 8

• repeated string hgvs = 9

• string display_consequence_type = 10

• repeated ConsequenceType consequence_types = 11

• repeated PopulationFrequency population_frequencies = 12

• string minorAllele = 13

• float minorAlleleFreq = 14

• repeated Score conservation = 15

• repeated Expression gene_expression = 16

• repeated GeneTraitAssociation gene_trait_association = 17

• repeated GeneDrugInteraction gene_drug_interaction = 18

• repeated Constraint gene_constraints = 26

• repeated EvidenceEntry trait_association = 24

• repeated Score functional_score = 20

• repeated Repeat repeat = 21

• repeated Cytoband cytoband = 22

• repeated Drug drugs = 25

• repeated GeneMirnaTarget gene_mirna_targets = 27

• repeated GeneCancerAssociation gene_cancer_associations = 28

• repeated Pharmacogenomics pharmacogenomics = 29

• repeated GwasAssociation gwas = 30

• repeated CancerHotspotVariantAnnotation cancer_hotspots = 31

• repeated PolygenicScoreAnnotation polygenicScores = 32

• repeated GeneImprinting geneImprinting = 33

• repeated GeneFusionSummary geneFusions = 34

• optional GenomicSequenceContext genomic_sequence_context = 35

• map<string, VariantAnnotation.AdditionalAttribute> additional_attributes = 23

Used in: VariantAnnotation

• map<string, string> attribute = 1

Used in: VariantAnnotation

• string id = 1

• string source = 2

* The variant classification according to different properties.

Used in: EvidenceEntry

• ClinicalSignificance clinicalSignificance = 1

  * The variant's clinical significance.

• DrugResponseClassification drugResponseClassification = 2

  * The variant's pharmacogenomics classification.

• TraitAssociation traitAssociation = 3

  * The variant's trait association.

• TumorigenesisClassification tumorigenesisClassification = 4

  * The variant's tumorigenesis classification.

• VariantFunctionalEffect functionalEffect = 5

  * The variant functional effect

• string fileId = 1

• string studyId = 2

• string fileName = 3

• string studyName = 4

• repeated string samples = 5

• map<string, string> metadata = 6

* Variant effect with Sequence Ontology terms. `SO_0002052`: dominant_negative_variant (http://purl.obolibrary.org/obo/SO_0002052) `SO_0002053`: gain_of_function_variant (http://purl.obolibrary.org/obo/SO_0002053) `SO_0001773`: lethal_variant (http://purl.obolibrary.org/obo/SO_0001773) `SO_0002054`: loss_of_function_variant (http://purl.obolibrary.org/obo/SO_0002054) `SO_0001786`: loss_of_heterozygosity (http://purl.obolibrary.org/obo/SO_0001786) `SO_0002055`: null_variant (http://purl.obolibrary.org/obo/SO_0002055)

Used in: VariantClassification

• dominant_negative_variant = 0

• gain_of_function_variant = 1

• lethal_variant = 2

• loss_of_function_variant = 3

• loss_of_heterozygosity = 4

• null_variant = 5

Used in: StudyEntry

• string id = 1

  * Variant score ID.

• string cohort1 = 2

  * Main cohort used for calculating the score.

• string cohort2 = 3

  * Optional secondary cohort used for calculating the score.

• float score = 4

  * Score value

• float pValue = 5

  * Score p value

Used in: StudyEntry

• string cohortId = 17

  * Unique cohort identifier within the study.

• int32 sampleCount = 18

  * Count of samples with non-missing genotypes in this variant from the cohort. This value is used as denominator for genotypeFreq.

• int32 fileCount = 19

  * Count of files with samples from the cohort that reported this variant. This value is used as denominator for filterFreq.

• int32 alleleCount = 1

  * Total number of alleles in called genotypes. It does not include missing alleles. This value is used as denominator for refAlleleFreq and altAlleleFreq.

• int32 refAlleleCount = 2

  * Number of reference alleles found in this variant.

• int32 altAlleleCount = 3

  * Number of main alternate alleles found in this variants. It does not include secondary alternates.

• float refAlleleFreq = 4

  * Reference allele frequency calculated from refAlleleCount and alleleCount, in the range [0,1]

• float altAlleleFreq = 5

  * Alternate allele frequency calculated from altAlleleCount and alleleCount, in the range [0,1]

• int32 missingAlleleCount = 8

  * Number of missing alleles

• int32 missingGenotypeCount = 9

  * Number of genotypes with all alleles missing (e.g. ./.). It does not count partially missing genotypes like "./0" or "./1".

• map<string, int32> genotypeCount = 6

  * Number of occurrences for each genotype. This does not include genotype with all alleles missing (e.g. ./.), but it includes partially missing genotypes like "./0" or "./1". Total sum of counts should be equal to the count of samples.

• map<string, float> genotypeFreq = 7

  * Genotype frequency for each genotype found calculated from the genotypeCount and samplesCount, in the range [0,1] The sum of frequencies should be 1.

• map<string, int32> filterCount = 14

  * The number of occurrences for each FILTER value in files from samples in this cohort reporting this variant. As each file can contain more than one filter value (usually separated by ';'), the total sum of counts could be greater than to the count of files.

• map<string, float> filterFreq = 15

  * Frequency of each filter calculated from the filterCount and filesCount, in the range [0,1]

• int32 qualityCount = 20

  * The number of files from samples in this cohort reporting this variant with valid QUAL values. This value is used as denominator to obtain the qualityAvg.

• float qualityAvg = 16

  * The average Quality value for files with valid QUAL values from samples in this cohort reporting this variant. Some files may not have defined the QUAL value, so the sampling could be less than the filesCount.

• float maf = 10

  * Minor allele frequency. Frequency of the less common allele between the reference and the main alternate alleles. This value does not take into acconunt secondary alternates.

• float mgf = 11

  * Minor genotype frequency. Frequency of the less common genotype seen in this variant. This value takes into account all values from the genotypeFreq map.

• string mafAllele = 12

  * Allele with minor frequency

• string mgfGenotype = 13

  * Genotype with minor frequency

* Type of variation, which depends mostly on its length. <ul> <li>SNVs involve a single nucleotide, without changes in length</li> <li>MNVs involve multiple nucleotides, without changes in length</li> <li>Indels are insertions or deletions of less than SV_THRESHOLD (50) nucleotides</li> <li>Structural variations are large changes of more than SV_THRESHOLD nucleotides</li> <li>Copy-number variations alter the number of copies of a region</li> </ul>

Used in: AlternateCoordinate, Variant, VcfRecord

• NO_VARIATION = 0

  As the NO_VARIATION is the most common value on gVCFs, being the first value, protobuf will use this as default value and save some space.

  Defined in HTSJDK

• SNV = 2

  SO:0001483

• MNV = 4

  SO:0002007

• INDEL = 5

  SO:1000032

• SV = 6

  SO:0001537

• COPY_NUMBER = 7

  SO:0001019

• COPY_NUMBER_GAIN = 16

  SO:0001742

• COPY_NUMBER_LOSS = 17

  SO:0001743

• SYMBOLIC = 8

  Defined in HTSJDK

• MIXED = 9

  Defined in HTSJDK

• INSERTION = 10

  SO:0000667

• DELETION = 11

  SO:0000159

• TRANSLOCATION = 12

  SO:0000199

• INVERSION = 13

  SO:1000036

• DUPLICATION = 14

  SO:1000035

• TANDEM_DUPLICATION = 18

  SO:1000173

• BREAKEND = 15

• CNV = 20

  Deprecated

  Deprecated. Renamed to COPY_NUMBER

• SNP = 1

  Deprecated

• MNP = 3

  Deprecated

Used in: VcfSlice

• int32 relative_start = 1

  1 based May contain negative values but it's not likely

• int32 relative_end = 2

  May contain negative values but it's not likely

• string reference = 3

• string alternate = 4

• float quality = 5

• VariantType type = 12

• string call = 13

• uint32 filter_index = 6

• repeated string id_non_default = 7

• repeated uint32 info_key_index = 8

• repeated string info_value = 9

• uint32 formatIndex = 10

• repeated VcfSample samples = 11

• repeated AlternateCoordinate secondaryAlternates = 14

Used in: VcfRecord

• repeated string sample_values = 1

• uint32 gt_index = 2

  GT is mandatory. Saving it separately can create a map of genotypes in Fields

• string chromosome = 1

• uint32 position = 2

• repeated VcfRecord records = 3

  List of records (lines)

• optional Fields fields = 4

Used in: Transcript

• string id = 1

• string db_name = 2

• string db_display_name = 3

• string description = 4