ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-75G>C (rs63750400)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000029959 SCV000052614 uncertain significance not specified 2019-01-16 criteria provided, single submitter clinical testing Variant summary: The variant, HBB c.-75G>C is located 25 nucleotides upstream of the HBB gene in the untranscribed promoter region, near the conserved TATA box (nucleotide positions -32 to -26 from transcription initiation site), which is known to be involved in transcriptional regulation. The variant allele was found at a frequency of 3.2e-05 in 30964 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant c.-75G>C has been reported in the literature in one individual affected by sickle cell / beta+ thalassemia (Eng_2007). A recent publication also reported another variant affecting the same nucleotide position (i.e. c.-75G>T) as a cause of BTHAL, indicating the functional importance of this nucleotide location (Li_2015; PMID: 25657036). 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. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508639 SCV000605835 likely pathogenic not provided 2017-05-15 criteria provided, single submitter clinical testing

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