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(F9):c.60A>G (p.Leu20=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10529715

701352 (ClinVar)

Gene: F9

Condition: hemophilia B

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: a1170f31-d66e-4804-818f-4fc81a684a07

Approved on: 2024-02-09

Published on: 2024-07-11

HGVS expressions

NM_000133.4:c.60A>G

NM_000133.4(F9):c.60A>G (p.Leu20=)

NC_000023.11:g.139530824A>G

CM000685.2:g.139530824A>G

NC_000023.10:g.138612983A>G

CM000685.1:g.138612983A>G

NC_000023.9:g.138440649A>G

NG_007994.1:g.5089A>G

ENST00000218099.7:c.60A>G

ENST00000218099.6:c.60A>G

ENST00000394090.2:c.60A>G

ENST00000479617.2:n.67A>G

NM_000133.3:c.60A>G

NM_001313913.1:c.60A>G

NM_001313913.2:c.60A>G

Benign

BA1 BP7 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_000133.4(F9):c.60A>G (p.Leu20=) synonymous variant is reported at an MAF of 0.0009351 (7/7486 alleles) in the Ashkenazi Jewish population in gnomAD v2.1.1 with 4 hemizygotes, meeting BA1 criteria of MAF > 0.0000556. SpliceAI predicts no splicing impact with a score of 0.0, meeting BP4 and BP7 criteria (<0.01). In summary, based on the evidence available at this time, the clinical significance of this variant is benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F9: BA1, BP4 and BP7.

BA1

The c.60A>G (p.Leu20=) variant is reported at an MAF of 0.0009351 (7/7486 alleles) in the Ashkenazi Jewish population in gnomAD v2.1.1 with 4 hemizygotes, meeting BA1 criteria of MAF > 0.0000556. However, it is unclear if inbred populations should be considered. The variant is also reported at an MAF of 0.00001226 (1/81585 alleles) in the non-Finnish European population in gnomAD v2.1.1 with 1 hemizygote, which does not meet BA1 criteria. BA1 is applied but has to be verified with experts that inbred populations may be used for BA1/BS1.

BP7

SpliceAI predicts no splicing impact with a score of 0.0, meeting BP7 criteria (<0.01). The variant meets the conservation thresholds with scores of -0.22 for PhyloP (<0.1) and 0.96 for PhastCons (<1).

BP4

The synonymous variant does not have a REVEL score. SpliceAI predicts no splicing impact with a score of 0.0, meeting BP4 criteria (<0.01)

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.