ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.45G>A (p.Leu15=) (rs762782573)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508663 SCV000605838 uncertain significance not specified 2017-06-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000508663 SCV000919462 likely benign not specified 2018-06-05 criteria provided, single submitter clinical testing Variant summary: HBB c.45G>A alters a non-conserved nucleotide resulting in a synonymous change. HBB c.45G>A results 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 3.3e-05 in 245982 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.45G>A has been reported in the literature in individuals affected with Hemoglobinopathy and has been reported in 12 individuals with low MCV and MCH values in cis with Hb Sheffield (i.e., p.Pro59His). In all of these individuals, their low MCV and MCH values were explained by an alpha gene deletion (Zadjali_2011), suggesting the variant was likely not the cause of disease. 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. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

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