{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/1d551fc0-d415-4840-99f9-66e331949130/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "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/CA034017/MONDO:0007750/013/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/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": "2024/10/2", "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/CA034017/MONDO:0007750/013/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA034017/MONDO:0007750/013/ci/CA034017/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": "PopMax MAF=0.00003 in South Asian population in gnomAD (gnomAD v2.1.1).", "contributionDate": { "date": "2024/10/2", "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": "CA034017/MONDO:0007750/013/ci/CA034017/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/MONDO:0007750/013/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/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": "2024/10/2", "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/CA034017/MONDO:0007750/013/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA034017/MONDO:0007750/013/ci/CA034017/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": "Two other variants at same codon: LDLR:c.1367T>C (p.Leu456Pro) classified as VUS; LDLR:c.1367T>A(p.Leu456His) classified as VUS by these guidelines, therefore PM5 is not met. ", "contributionDate": { "date": "2024/10/2", "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": "CA034017/MONDO:0007750/013/ci/CA034017/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/MONDO:0007750/013/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/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": "2024/10/2", "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/CA034017/MONDO:0007750/013/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA034017/MONDO:0007750/013/ci/CA034017/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 is not available.", "contributionDate": { "date": "2024/10/2", "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": "CA034017/MONDO:0007750/013/ci/CA034017/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/MONDO:0007750/013/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/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": "2024/10/2", "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/CA034017/MONDO:0007750/013/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA034017/MONDO:0007750/013/ci/CA034017/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=0.487, it is not above 0.75, splicing evaluation required. \nFunctional data on splicing is not available. MES performed:\nA) Variant is not on limits.\nB) Variant is on limit but does not crate de novo AG. Variant created GT however is not on limit. \nC) Variant is on limit and nearby three intra-exonic AGs: cctcctgcctcagcacccAGc/ttt , Var/Wt cryptic score = 0.37/-0.2 = -0.15, it is <1.1; ctcagcacccagc/tttgacAGagc, Var/Wt cryptic score = -3.2/-2.9 = 1.103, it is = 1.1, however both scores are negative; and agcacccagc/tttgacagAGccc, Var/Wt cryptic score = -33.4/-34.48 = 0.97, it is <1.1. MES score for canonical intron 9 acceptor cttctctcctcctgcctcAGcac is 6.76, so none of the Var cryptic scores/Wt score is >0.9. Variant is not predicted to alter splicing. REVEL score is below 0.5, therefore BP4 is met. SpliceAI confirmed same result.\n", "contributionDate": { "date": "2024/10/2", "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": "CA034017/MONDO:0007750/013/ci/CA034017/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/MONDO:0007750/013/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA034017/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": "2024/10/2", "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/CA034017/MONDO:0007750/013/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA034017/MONDO:0007750/013/ci/CA034017/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 is not available.", "contributionDate": { "date": "2024/10/2", "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": "CA034017/MONDO:0007750/013/ci/CA034017/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA034017/MONDO:0007750/013", "metadata": { "created": "2024-10-02T02:42:18.606Z", "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": "Wed, 02 Oct 2024 02:42:18 -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": "1d551fc0-d415-4840-99f9-66e331949130", "variant": { "@id": "https://reg.genome.network/allele/CA034017", "id": "CAR:CA034017", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000527.5:c.1366C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000527.5(LDLR):c.1366C>T (p.Leu456Phe)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-09T10:13:44.377Z" } }, "status": { "code": 200, "name": "OK" } }