{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/33ebf93f-ff2f-4ffc-9e03-d880c84e3fc6/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/CA003698/MONDO:0700268/092/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003698/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": "2026/8/27", "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/CA003698/MONDO:0700268/092/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003698/MONDO:0700268/092/ci/CA003698/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 2 calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 30209399, 35196514) (PS3 met).\n", "contributionDate": { "date": "2026/8/27", "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": "CA003698/MONDO:0700268/092/ci/CA003698/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003698/MONDO:0700268/092/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003698/MONDO:0700268/092/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/8/27", "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/CA003698/MONDO:0700268/092/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003698/MONDO:0700268/092/ci/CA003698/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 0.2795, indicating impact on BRCA1 function via protein change is unclear (score range 0.15-0.28). A SpliceAI score of 0 predicts no impact on splicing (score threshold ≤0.1) (no bioinformatic code is applied).\n", "contributionDate": { "date": "2026/8/27", "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": "CA003698/MONDO:0700268/092/ci/CA003698/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1654", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003698/MONDO:0700268/092/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003698/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": "2026/8/27", "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/CA003698/MONDO:0700268/092/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003698/MONDO:0700268/092/ci/CA003698/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": "2026/8/27", "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": "CA003698/MONDO:0700268/092/ci/CA003698/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003698/MONDO:0700268/092/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003698/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": "2026/8/27", "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/CA003698/MONDO:0700268/092/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003698/MONDO:0700268/092/ci/CA003698/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 a SpliceAI score of 0 predicts no impact on splicing (score threshold ≤0.1). The computational predictor BayesDel (noAF) gives a score of 0.28, equal to or above the recommended threshold of 0.28 for prediction of impact on BRCA1 function via protein change (PP3 met).\n", "contributionDate": { "date": "2026/8/27", "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": "CA003698/MONDO:0700268/092/ci/CA003698/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092/0/1747", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003698/MONDO:0700268/092", "metadata": { "created": "2026-08-27T23:24:36.851Z", "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": "Thu, 27 Aug 2026 23:24:36 -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": "33ebf93f-ff2f-4ffc-9e03-d880c84e3fc6", "variant": { "@id": "https://reg.genome.network/allele/CA003698", "id": "CAR:CA003698", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_007294.4:c.5528C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_007294.4(BRCA1):c.5528C>A (p.Ala1843Glu)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-13T20:10:17.130Z" } }, "status": { "code": 200, "name": "OK" } }