Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000133.3(F9):c.88+5G>T

CA915952341

627156 (ClinVar)

Gene: F9 (HGNC:2158)

Condition: hemophilia B (MONDO:0010604)

Inheritance Mode: X-linked inheritance

UUID: 67d79118-0240-41eb-a752-48b2d3ccaf41

Approved on: 2025-03-10

Published on: 2025-03-28

HGVS expressions

NM_000133.3:c.88+5G>T

NM_000133.3(F9):c.88+5G>T

NC_000023.11:g.139530857G>T

CM000685.2:g.139530857G>T

NC_000023.10:g.138613016G>T

CM000685.1:g.138613016G>T

NC_000023.9:g.138440682G>T

NG_007994.1:g.5122G>T

ENST00000218099.7:c.88+5G>T

ENST00000218099.6:c.88+5G>T

ENST00000394090.2:c.88+5G>T

ENST00000479617.2:n.95+5G>T

NM_001313913.1:c.88+5G>T

NM_000133.4:c.88+5G>T

NM_001313913.2:c.88+5G>T

Likely Pathogenic

PS4 PP3 PM2_Supporting

Evidence Links 0

Expert Panel

Coagulation Factor Deficiency VCEP

Criteria Specification Information

Criteria Specification: ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Coagulation Factor Deficiency VCEP

The F9: c.88+5G>T variant is completely absent in population databases (gnomAD v2.1.1/gnomAD v3.1.2) meeting PM2_Supporting. This intronic variant is predicted to alter splicing based on SpliceAI prediction that the canonical donor site is lost, with a score of 0.91 (>0.5) meeting PP3 criteria. It has been reported in at least 4 probands in the literature with moderate to severe hemophilia B meeting phenotypic criteria for F9 (PMIDs: 31064749, 9452115, 10094553). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8/F9: PS4, PP3, PM2_Supporting.

PS4

The c.88+5G>T variant has been reported in at least 4 probands in the literature with moderate to severe hemophilia B (0 gnomAD alleles) meeting phenotypic criteria for F9.

PP3

The c.88+5G>T intronic variant is predicted to alter splicing based on SpliceAI prediction of canonical donor site loss with score of 0.91 (threshold >0.5)

PM2_Supporting

The c.88+5G>T variant is completely absent in population databases (gnomAD v2.1.1/gnomAD v3).

Curation History

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