ClinVar Miner

Submissions for variant NM_000133.4(F9):c.-35G>A

gnomAD frequency: 0.00001  dbSNP: rs1166164399
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795083 SCV000934525 pathogenic Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect 2019-06-17 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the F9 gene. It does not change the encoded amino acid sequence of the F9 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with hemophilia B Leyden in families (PMID: 7677806, 2352926) and has been observed in several unrelated affected individuals (PMID: 28168417, 2352926, 8251390, 10595634, 7734378, 8217825). This variant is also known as -6G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 10559). This variant has been reported to affect F9 protein function (PMID: 23472758, 2352926). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004586929 SCV005076562 pathogenic Hereditary factor IX deficiency disease 2024-04-24 criteria provided, single submitter clinical testing Variant summary: F9 c.-35G>A is located in the untranscribed region upstream of the F9 gene region. The variant was absent in 182805 control chromosomes. c.-35G>A (also known as -6G>A) has been reported in the literature in multiple individuals affected with hemophilia B Leydenin and segregated with disease in at least one family (e.g. Coyle_1994, Ahmed_2020, Hirosawa_1990, Tamura_2021). These data indicate that the variant is very likely to be associated with disease. Experimental studies show that this variant reduce the expression level of factor IX (Hirosawa_1990, Funnell_2013). The following publications have been ascertained in the context of this evaluation (PMID: 32346856, 7677806, 23472758, 2352926, 33427373). ClinVar contains an entry for this variant (Variation ID: 641767). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV001815011 SCV000031533 pathogenic Hemophilia B leyden 1990-08-11 no assertion criteria provided literature only

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