{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/3b97275b-1610-4c8c-aa33-afd4f5c09395/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1527859052", "label": "ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 2.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010604", "id": "MONDO:0010604", "label": "hemophilia B", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "contributionDate": { "date": "2026/4/12", "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/CA414434503/MONDO:0010604/080/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "comments": "PMID: 32766856 analyzed variants in a cell-based reporter assay with levels of secreted conformation-specific reporter with a functional γ-carboxyglutamate (Gla) domain of FIX. The Val30Leu variant showed less secretion of functional protein. The actual levels of FIX:C and FIX:Ag are not available; however, since this assay has been accepted as valid by the CFD VCEP, PS3_Supporting criteria is met.\n\n", "contributionDate": { "date": "2026/4/12", "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": "CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/el/0/1786", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/ei/1/1787", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "contributionDate": { "date": "2026/4/12", "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/CA414434503/MONDO:0010604/080/el/0/1786/1788", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "comments": "Val30Ile is a variant at the same residue and is classified as likely pathogenic by the CFD-VCEP yet. Both Val30Leu and Val30Ile are predicted to impact splicing. The computational splicing predictor SpliceAI gives a score of 0.97 for donor loss, predicting that the variant disrupts the donor splice site of intron 1 of F9. For the F9 c.88G>A, p.Val30Ile variant, the computational splicing predictor SpliceAI gives a score of 0.96 for donor loss.", "contributionDate": { "date": "2026/4/12", "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": "CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1786/1788", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/1/1787", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1786", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "contributionDate": { "date": "2026/4/12", "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/CA414434503/MONDO:0010604/080/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "comments": "The c.88G>C (p.Val30Leu) missense variant has a REVEL score of 0.787 (>0.6). The variant affects the last codon of exon 1 and spliceAI predicts a splicing impact with delta score of 0.97. ", "contributionDate": { "date": "2026/4/12", "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": "CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "contributionDate": { "date": "2026/4/12", "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/CA414434503/MONDO:0010604/080/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "comments": "The c.88G>C; p.Val30Leu variant is completely absent from gnomAD v4.1.1.", "contributionDate": { "date": "2026/4/12", "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": "CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA414434503/MONDO:0010604/080/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "contributionDate": { "date": "2026/4/12", "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/CA414434503/MONDO:0010604/080/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50041_EP17152769886754", "id": "CG-PCER-AGENT:CG_50041_EP17152769886754", "type": "Agent" }, "comments": "1 proband with the Val30Leu variant and moderate hemophilia B is reported in the literature (PMID: 31064749) and 1 proband with severe hemophilia B is listed in the EAHAD factor IX (F9) database.", "contributionDate": { "date": "2026/4/12", "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": "CA414434503/MONDO:0010604/080/ci/CA414434503/MONDO:0010604/080.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080/0/1699", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA414434503/MONDO:0010604/080", "metadata": { "created": "2026-04-12T17:40:46.619Z", "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": "Sun, 12 Apr 2026 17:40:42 -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": "3b97275b-1610-4c8c-aa33-afd4f5c09395", "variant": { "@id": "https://reg.genome.network/allele/CA414434503", "id": "CAR:CA414434503", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000133.3:c.88G>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000133.3(F9):c.88G>C (p.Val30Leu)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-27T07:33:40.360Z" } }, "status": { "code": 200, "name": "OK" } }