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_000133.4:c.712T>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10529821

1166447 (ClinVar)

Gene: F9

Condition: hemophilia B

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 3b02dca7-ec7c-43b8-a80b-8da7a82a2691

Approved on: 2024-02-09

Published on: 2024-07-11

HGVS expressions

NM_000133.4:c.712T>G

NC_000023.11:g.139551253T>G

CM000685.2:g.139551253T>G

NC_000023.10:g.138633412T>G

CM000685.1:g.138633412T>G

NC_000023.9:g.138461078T>G

NG_007994.1:g.25518T>G

ENST00000218099.7:c.712T>G

ENST00000643157.1:n.1379T>G

ENST00000218099.6:c.712T>G

ENST00000394090.2:c.598T>G

NM_000133.3:c.712T>G

NM_001313913.1:c.598T>G

NM_001313913.2:c.598T>G

Benign

BA1

PP3 PS4 BP4

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 NM_000133.3:c.712T>G predicts a missense variant, Phe238Val, that is reported at a high MAF of 0.0008074 (12/14862 alleles with 4 hemizygotes) in the East Asian population of gnomAD v2.1.1, meeting the BA1 cut-off of >= 0.0000556. It is reported in the literature in at least one severe Hemophilia B patient who has an additional F9 variant. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency VCEP for F9: BA1.

BA1

Phe238Val is reported in gnomAD v2.1.1 at a frequency of 0.0008074 (12/14862 alleles with 4 hemizygotes) in the East Asian population and in gnomAD v3 at a frequency of 0.00005947 (3/50446 alleles with 1 hemizygote) in the NFE population. gnomAD V2.1.1 MAF meets the BA1 threshold for F9 (>= 0.0000556).

PP3

REVEL score of 0.547 and CADD score of 18.80 do not meet threshold for PP3 (REVEL >0.6; CADD >21)

PS4

The variant has been reported in at least 1 individual of Taiwanese origin. PS4 is not considered while BA1 is met.

BP4

REVEL score of 0.547 and CADD score of 18.80 do not meet threshold for BP4 (REVEL <0.3; CADD <11)

Curation History

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