ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-51T>C (rs386134236)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000029958 SCV000052613 uncertain beta Thalassemia 2011-08-18 criteria provided, single submitter curation Converted during submission to Uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000781449 SCV000919485 uncertain significance not specified 2018-09-27 criteria provided, single submitter clinical testing Variant summary: HBB c.-51T>C is located in the untranscribed region upstream of the HBB gene region, one nucleotide upstream from the transcription initiation site (also known as mRNA cap site), therefore the variant might affect gene expression. One in silico tool predicts a damaging outcome for the variant. 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 0.00017 in 274970 control chromosomes, predominantly within the African subpopulation at a frequency of 0.002 in the gnomAD database. This frequency is not higher than expected for a pathogenic variant in HBB causing Hemoglobinopathy (0.00017 vs 0.011), allowing no conclusion about variant significance. The variant, c.-51T>C, has been reported in the literature in one individual without strong evidence for causality (Kunz 2016). This report does not provide unequivocal conclusions about association of the variant with Hemoglobinopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759800 SCV000889374 uncertain significance not provided 2017-11-28 criteria provided, single submitter clinical testing

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