ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-151C>T (rs63751208)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169081 SCV000220255 pathogenic beta Thalassemia 2014-04-17 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000169081 SCV000697087 pathogenic beta Thalassemia 2017-08-07 criteria provided, single submitter clinical testing Variant summary: c.-151C>T affects a non-conserved nucleotide in the promoter of HBB gene. Mutation Taster predicts a damaging outcome for this variant. This prediction was confirmed by a CAT promoter activity assay showing that this variant decreased promoter activity by 70% (Gonzalez-Redondo_1989). This variant was found in 1/31016 control chromosomes at a frequency of 0.0000322, which does not exceed the estimated maximal expected allele frequency of a pathogenic HBB variant (0.0111803). This variant is a well-known pathogenic HBB variant and has been reported in more than thirty unrelated patients with b-thalassemia intermedia. In addition, multiple clinical laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Invitae RCV000820736 SCV000961462 pathogenic not provided 2019-12-31 criteria provided, single submitter clinical testing This sequence change falls in the promoter of the HBB gene. It does not change the encoded amino acid sequence of the HBB protein, but has been reported to disrupt HBB transcription. This variant has been observed to segregate with HBB-related conditions in several families and has been observed in many unrelated affected individuals (PMID: 2713503, 10606872, 2001456). This variant is also known as -101C>T. ClinVar contains an entry for this variant (Variation ID: 15461). Experimental studies have shown that this promoter change has a deleterious effect on transcription (PMID: 2713503). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000016719 SCV000036989 pathogenic Beta-plus-thalassemia 1999-12-01 no assertion criteria provided literature only
GeneReviews RCV000169081 SCV000537286 pathogenic beta Thalassemia 2015-05-14 no assertion criteria provided literature only

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