ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-50A>C (rs34305195)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000029957 SCV000537293 pathogenic beta Thalassemia 2015-05-14 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000029957 SCV000052612 pathogenic beta Thalassemia 2017-02-08 criteria provided, single submitter clinical testing Variant summary: The HBB c.-50A>C (also known as CAP +1 A>C) variant involves the alteration of a non-conserved nucleotide, which lies in the CAP-site from where transcription starts. One in silico tool predicts a damaging outcome for this variant. This variant was found in 12/119792 control chromosomes at a frequency of 0.0001002, which does not exceed the estimated maximal expected allele frequency of a pathogenic HBB variant (0.0111803). The variant was reported in numerous Beta Thalassemia patients individuals in the literature. Taken together, this variant is classified as pathogenic.
Invitae RCV000508619 SCV000937271 likely pathogenic not provided 2018-12-24 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the HBB gene. It does not change the encoded amino acid sequence of the HBB protein. This variant is present in population databases (rs34305195, ExAC 0.07%). This variant has been observed in individuals affected with beta thalassemia (PMID: 19254853, 22335963, 27263053). It is also known as the "Cap+1" or "Cap site+1" variant in the literature. ClinVar contains an entry for this variant (Variation ID: 36292). Experimental studies have shown that this non-coding change causes a reduction in HBB mRNA expression (PMID: 3683554). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508619 SCV000605834 pathogenic not provided 2017-06-08 criteria provided, single submitter clinical testing

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