{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b74bd1df-6299-4165-81c4-df9cc4e12aea/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1530970787", "label": "ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA1 Version 1.2", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.2" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0700268", "id": "MONDO:0700268", "label": "BRCA1-related cancer predisposition", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.36, above the recommended threshold of 0.28 for prediction of impact on BRCA1 function via protein change. A SpliceAI score of 0 predicts no impact on splicing (score threshold <0.10) (PP3 met).", "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 4.28 (based on Co-occurrence LR=1.07; Family History LR=4.01), within the thresholds for supporting evidence towards pathogenicity (LR >2.08 & ≤4.3) (PP4 met; Internal lab contributor). ", "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1 (read depth ≥25x in >90% samples, PM2_Supporting met).", "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003398/MONDO:0700268/092/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "comments": "Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 30209399, 30765603). This variant is reported as showing discrepant results in PMID: 32546644 and the authors recommend further investigation before using their results, therefore this assay has been excluded from the assessment of functional data (PS3 met).", "contributionDate": { "date": "2026/7/24", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA003398/MONDO:0700268/092/ci/CA003398/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092/0/1828", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003398/MONDO:0700268/092", "metadata": { "created": "2026-07-24T03:55:43.829Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Fri, 24 Jul 2026 03:55:43 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "b74bd1df-6299-4165-81c4-df9cc4e12aea", "variant": { "@id": "https://reg.genome.network/allele/CA003398", "id": "CAR:CA003398", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_007294.4:c.5258G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_007294.4(BRCA1):c.5258G>C (p.Arg1753Thr)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-03T18:26:32.276Z" } }, "status": { "code": 200, "name": "OK" } }