{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/c0051ae4-c173-42f5-9416-90f68e29222d/doc/sepio/version/1.1.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/639509375", "label": "ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ACADVL Version 2.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0008723", "id": "MONDO:0008723", "label": "very long chain acyl-CoA dehydrogenase deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2026/1/21", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "Four patients compound heterozygous for the variant and distinct pathogenic or likely pathogenic variant displayed increased C14:1 Levels (PMID: 25655073), or reduced enzyme levels to 0.69 C16/C8 (PMID: 15210884), below detection rate (PMID: 28755359), and 19.3% (PMID: 33150772) respectively, which is highly specific for VLCAD deficiency (PP4_Moderate)", "contributionDate": { "date": "2026/1/21", "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": "CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2026/1/21", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "This variant has been detected in at least 6 individuals with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. Of those individuals, 2 were compound heterozygous for the variant and distinct pathogenic or likely pathogenic variant and 1 of those were confirmed in trans by parental/family testing, other methods. No individuals were homozygous for the variant (PM3 points: 1.25) (PMID: 33150772, 28755359, 32655480, 15210884, 25655073, 16488171) (PM3)\n", "contributionDate": { "date": "2026/1/21", "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": "CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2026/1/21", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.91, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3).", "contributionDate": { "date": "2026/1/21", "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": "CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2026/1/21", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA239438/MONDO:0008723/021/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "The highest population minor allele frequency in gnomAD v4.1 is 0.00015 in the Admixed American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).\n", "contributionDate": { "date": "2026/1/21", "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": "CA239438/MONDO:0008723/021/ci/CA239438/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA239438/MONDO:0008723/021", "metadata": { "created": "2026-01-21T19:58:45.537Z", "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, 21 Jan 2026 19:58:45 -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": "c0051ae4-c173-42f5-9416-90f68e29222d", "variant": { "@id": "https://reg.genome.network/allele/CA239438", "id": "CAR:CA239438", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000018.4:c.1153C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000018.4(ACADVL):c.1153C>T (p.Arg385Trp)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T05:07:51.545Z" } }, "status": { "code": 200, "name": "OK" } }