ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.316-37G>T (rs193922559)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029986 SCV000052641 likely benign not specified 2021-03-22 criteria provided, single submitter clinical testing Variant summary: HBB c.316-37G>T is located at a deep intronic position. 4/4 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 0.00022 in 250358 control chromosomes, predominantly at a frequency of 0.003 within the African or African-American subpopulation in the gnomAD database. This frequency is not higher than expected for a pathogenic variant in HBB causing Hemoglobinopathy (0.011), allowing no conclusion about variant significance. The variant, c.316-37G>T, has been reported in the literature in an individual affected with mild B-thalassemia trait (Mason_2016), however this individual also carried a common pathogenic HBB variant (c.-79A>G; phase not specified), which could explain the phenotype. Four samples tested internally by our laboratory have been found to carry the variant, c.316-37G>T, in addition to two pathogenic HBB mutations, providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Deep intronic variants affecting this region have been reported in affected individuals as causative variants (e.g. c.316-106C>G, c.316-146T>G, c.316-197C>T). Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign (n=1) or likely benign(n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000978010 SCV001125934 benign not provided 2020-12-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282806 SCV001156555 likely benign none provided 2019-12-05 criteria provided, single submitter clinical testing

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