ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1167G>A (p.Thr389=) (rs139066906)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000775058 SCV000909158 likely benign Familial hypercholesterolemias 2017-07-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000249917 SCV000919592 uncertain significance not specified 2018-12-17 criteria provided, single submitter clinical testing Variant summary: LDLR c.1167G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00015 in 276906 control chromosomes, predominantly at a frequency of 0.0013 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in LDLR causing Familial Hypercholesterolemia phenotype (0.0013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant, c.1167G>A, has been reported in the literature in individuals affected with Familial Hypercholesterolemia as a benign polymorphism (Wintjens_2016). This report does not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic, while another laboratory classified it as likely benign at an unspecified date. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
PreventionGenetics RCV000249917 SCV000304682 likely benign not specified criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000495926 SCV000583796 likely pathogenic Familial hypercholesterolemia 2017-03-30 criteria provided, single submitter clinical testing

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