{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b4407a53-6c03-4cda-827d-40d769122dfd/doc/sepio/version/1.0.0", "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/CA003201/MONDO:0700268/092/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/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": "2026/9/21", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003201/MONDO:0700268/092/ci/CA003201/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 0.73, predicting an impact on splicing (score threshold ≥0.2) (PP3 not applied because a PVS1 (RNA) code is met).", "contributionDate": { "date": "2026/9/21", "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": "CA003201/MONDO:0700268/092/ci/CA003201/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/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": "2026/9/21", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003201/MONDO:0700268/092/ci/CA003201/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 3.065 (based on Co-occurrence LR=1.3848; Family History LR=2.213), above the thresholds for Supporting evidence towards pathogenicity (LR >2.08 & ≤4.3) (PP4 met; PMID 31853058, Internal lab contributors).", "contributionDate": { "date": "2026/9/21", "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": "CA003201/MONDO:0700268/092/ci/CA003201/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/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": "2026/9/21", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003201/MONDO:0700268/092/ci/CA003201/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": "2026/9/21", "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": "CA003201/MONDO:0700268/092/ci/CA003201/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/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": "2026/9/21", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003201/MONDO:0700268/092/ci/CA003201/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": "Missense variant shown to alter splicing (see PVS1 or BP7 for description), functional data considered only from assays that measure effect via mRNA and protein. Results from two calibrated studies with cDNA based design not considered for code application (PMIDs:38709234, 32546644). Reported by one calibrated study incorporating mRNA splicing effect to exhibit function similar to pathogenic control variants (PMID:30209399) (PS3 met).", "contributionDate": { "date": "2026/9/21", "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": "CA003201/MONDO:0700268/092/ci/CA003201/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1762", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/ei/1/1763", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844", "id": "CG-PCER-AGENT:CG_50087_EP169680482377844", "type": "Agent" }, "contributionDate": { "date": "2026/9/21", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0020", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0020", "label": "PVS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA003201/MONDO:0700268/092/el/0/1762/1764", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA003201/MONDO:0700268/092/ci/CA003201/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. Mini-gene demonstrated that the variant impacts splicing by out-of-frame skipping of exon 16(17) and in-frame retention of 153 bp of intron 16(17) (containing a premature stop codon and predicted to be non-functional) (PMID 25724305). The percent skipping of exon 16(17)/in-frame retention produced from the variant allele, estimated by measuring gel electrophoretic band intensities, was stated to be 25%/75%, no full-length transcript is produced by the variant allele and all transcripts produced are predicted to be non-functional. Final code strength determined by the rubric: PVS1_Strong (RNA).", "contributionDate": { "date": "2026/9/21", "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": "CA003201/MONDO:0700268/092/ci/CA003201/MONDO:0700268/092.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1762/1764", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/1/1763", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092/0/1762", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA003201/MONDO:0700268/092", "metadata": { "created": "2026-10-15T19:00:37.158Z", "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, 15 Oct 2026 19:00:36 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "b4407a53-6c03-4cda-827d-40d769122dfd", "variant": { "@id": "https://reg.genome.network/allele/CA003201", "id": "CAR:CA003201", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_007294.4:c.5074G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_007294.4(BRCA1):c.5074G>A (p.Asp1692Asn)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T05:45:17.830Z" } }, "status": { "code": 200, "name": "OK" } }