{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/1cf991f6-8acb-487b-be82-4115fea5b23a/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637573", "label": "ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2", "type": "VariantPathogenicityInterpretationGuideline", "url": "https://clinicalgenome.org/docs/clingen-familial-hypercholesterolemia-expert-panel-specifications-to-the-acmg-amp-variant-interpretation-guidelines-version-1-2/", "version": "1.2.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0007750", "id": "MONDO:0007750", "label": "hypercholesterolemia, familial", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2025/9/15", "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/CA2322775423/MONDO:0007750/013/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "The multi-nucleotide variant 19-1230880-TT-CC is observed once in at least 251454 total alleles from gnomAD (gnomAD v2.1.1). PopMax MAF for 19-11230880-T-C (NM_000527.5 (LDLR):c.1958T>C (p.Val653Ala) (CA305302665) is 0.00009921 (1/10080 alleles) in Ashkenazi Jewish population (gnomAD v2.1.1), whereas 19-11230881-T-C (NM_000527.5 (LDLR):c.1959T>C (p.Val653=) (ClinVar ID 252131) is a common variant with Grpmax FAF of 0.5225 (gnomAD v2.1.1).", "contributionDate": { "date": "2025/9/15", "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": "CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2025/9/15", "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/CA2322775423/MONDO:0007750/013/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "REVEL score for NM_000527.5 (LDLR):c.1958_1959delinsCC (p.Val653Ala) is not available; REVEL score for NM_000527.5 (LDLR):c.1958T>C (p.Val653Ala) is 0.546. Splicing evaluation for c.1958_1959delinsCC performed. MES: A) variant not on limits. B) Variant not on limit creating de novo acceptor; variant is on limit however does not create GT. C) there is not a GT nearby. Variant is not predicted to alter splicing, and this result is confirmed by SpliceAI.", "contributionDate": { "date": "2025/9/15", "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": "CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2025/9/15", "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/CA2322775423/MONDO:0007750/013/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Clinical data not available.", "contributionDate": { "date": "2025/9/15", "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": "CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2025/9/15", "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/CA2322775423/MONDO:0007750/013/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Three other missense variants in the same codon: NM_000527.5 (LDLR):c.1958T>G (p.Val653Gly) (ClinVar ID 252130), classified as VUS by these guidelines; NM_000527.5 (LDLR):c.1957G>T (p.Val653Phe) (ClinVar ID 252129), classified as VUS by these guidelines; NM_000527.5 (LDLR):c.1957G>A (p.Val653Ile) (ClinVar ID 628891), classified as VUS by these guidelines, therefore PM5 is not met.", "contributionDate": { "date": "2025/9/15", "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": "CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2025/9/15", "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/CA2322775423/MONDO:0007750/013/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "REVEL score for NM_000527.5 (LDLR):c.1958_1959delinsCC (p.Val653Ala) is not available; REVEL score for NM_000527.5 (LDLR):c.1958T>C (p.Val653Ala) is 0.546. Splicing evaluation for c.1958_1959delinsCC performed. MES: A) variant not on limits. B) Variant not on limit creating de novo acceptor; variant is on limit however does not create GT. C) there is not a GT nearby. Variant is not predicted to alter splicing, and this result is confirmed by SpliceAI.", "contributionDate": { "date": "2025/9/15", "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": "CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2025/9/15", "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/CA2322775423/MONDO:0007750/013/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Functional data not available.", "contributionDate": { "date": "2025/9/15", "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": "CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA2322775423/MONDO:0007750/013/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2025/9/15", "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/CA2322775423/MONDO:0007750/013/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Clinical data not available.", "contributionDate": { "date": "2025/9/15", "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": "CA2322775423/MONDO:0007750/013/ci/CA2322775423/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA2322775423/MONDO:0007750/013", "metadata": { "created": "2025-09-15T06:17:36.941Z", "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, 15 Sep 2025 06:17:36 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "1cf991f6-8acb-487b-be82-4115fea5b23a", "variant": { "@id": "https://reg.genome.network/allele/CA2322775423", "id": "CAR:CA2322775423", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000527.5:c.1958_1959delinsCC" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000527.5(LDLR):c.1958_1959delinsCC (p.Val653Ala)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T10:37:19.008Z" } }, "status": { "code": 200, "name": "OK" } }