{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/9ef5ebb6-b717-4061-8655-b7c3bf79b9a5/doc/sepio/version/1.1.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "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/CA10580532/MONDO:0700268/092/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10580532/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": "2026/3/19", "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/CA10580532/MONDO:0700268/092/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10580532/MONDO:0700268/092/ci/CA10580532/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 has a SpliceAI score of 0.95, predicting an impact on splicing (score threshold >0.20) (PP3 met). ", "contributionDate": { "date": "2026/3/19", "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": "CA10580532/MONDO:0700268/092/ci/CA10580532/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10580532/MONDO:0700268/092/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10580532/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": "2026/3/19", "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/CA10580532/MONDO:0700268/092/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10580532/MONDO:0700268/092/ci/CA10580532/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 v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met).", "contributionDate": { "date": "2026/3/19", "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": "CA10580532/MONDO:0700268/092/ci/CA10580532/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10580532/MONDO:0700268/092/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10580532/MONDO:0700268/092/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/3/19", "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/CA10580532/MONDO:0700268/092/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10580532/MONDO:0700268/092/ci/CA10580532/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": "The variant under assessment is located outside the canonical dinucleotide, and has been assigned PP3 based on splicing predictions. Another variant at the same nucleotide position (c.4185G>A) is classified as pathogenic by the ENIGMA BRCA1/2 VCEP. The SpliceAI predictions indicate that the two variants are likely to lead to the same event (disruption of the donor splice site of intron 11(12) in BRCA1). These observations suggest that the variant has an impact on splicing consistent with pathogenicity (PS1 (Splicing) met).", "contributionDate": { "date": "2026/3/19", "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": "CA10580532/MONDO:0700268/092/ci/CA10580532/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10580532/MONDO:0700268/092/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10580532/MONDO:0700268/092/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/3/19", "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/CA10580532/MONDO:0700268/092/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10580532/MONDO:0700268/092/ci/CA10580532/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 reported to result in aberrant mRNA splicing. RT-PCR demonstrated that the variant impacts splicing by skipping of exon 12 (PMID: 29750258). The percent reference (full length) and aberrant transcripts produced from the variant allele is not stated (PVS1_N/A (RNA)).", "contributionDate": { "date": "2026/3/19", "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": "CA10580532/MONDO:0700268/092/ci/CA10580532/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092/0/1594", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10580532/MONDO:0700268/092", "metadata": { "created": "2026-03-19T01:42:33.496Z", "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, 19 Mar 2026 01:42:33 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.1.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "9ef5ebb6-b717-4061-8655-b7c3bf79b9a5", "variant": { "@id": "https://reg.genome.network/allele/CA10580532", "id": "CAR:CA10580532", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_007294.4:c.4185G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_007294.4(BRCA1):c.4185G>C (p.Gln1395His)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-03T11:29:01.732Z" } }, "status": { "code": 200, "name": "OK" } }