{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d883da51-7056-4ff2-b2fa-7e196697c22c/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/94412666", "label": "ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for AIPL1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100438", "id": "MONDO:0100438", "label": "AIPL1-related retinopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA8328680/MONDO:0100438/208/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This is a frameshift variant that introduces a premature stop codon into exon 1 of 6 and is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PVS1).\n", "contributionDate": { "date": "2025/9/29", "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": "CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA8328680/MONDO:0100438/208/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "Patient diagnosed with LCA (0.5 pts), no additional phenotype description.", "contributionDate": { "date": "2025/9/29", "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": "CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA8328680/MONDO:0100438/208/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who harbored the variant in the compound heterozygous state (PMID: 32531858). However, the proband was not counted for this criterion because the other variant p.Arg80Trp is currently classified as a VUS and was not confirmed to be in trans. PM3_Supporting requires at least 0.5 total points, so this criterion was not met.\n", "contributionDate": { "date": "2025/9/29", "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": "CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA8328680/MONDO:0100438/208/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "contributionDate": { "date": "2025/9/29", "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/CA8328680/MONDO:0100438/208/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166", "id": "CG-PCER-AGENT:CG_50082_EP170326324571166", "type": "Agent" }, "comments": "This variant is present in gnomAD v.4.1.0 at a total allele frequency of 0.000001859, with 3 /1614036 total alleles, which is lower than the ClinGen LCA/eoRD VCEP PM2_Supporting threshold of <0.0004 (PM2_Supporting).\n", "contributionDate": { "date": "2025/9/29", "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": "CA8328680/MONDO:0100438/208/ci/CA8328680/MONDO:0100438/208.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA8328680/MONDO:0100438/208", "metadata": { "created": "2025-09-29T17:54:29.044Z", "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": "Mon, 29 Sep 2025 17:54:28 -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": "d883da51-7056-4ff2-b2fa-7e196697c22c", "variant": { "@id": "https://reg.genome.network/allele/CA8328680", "id": "CAR:CA8328680", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_014336.5:c.34dup" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_014336.5(AIPL1):c.34dup (p.Val12fs)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-15T04:49:53.700Z" } }, "status": { "code": 200, "name": "OK" } }