ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-142C>T

dbSNP: rs34883338
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Total submissions: 4
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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 RCV000589915 SCV000697082 pathogenic Beta thalassemia intermedia 2023-08-23 criteria provided, single submitter clinical testing Variant summary: HBB c.-142C>T is located in the untranscribed region upstream of the HBB gene region. The variant was absent in 31398 control chromosomes (gnomAD). c.-142C>T has been reported in the literature in bi-allelic individuals affected with Beta Thalassemia Intermedia (examples: Rosatelli_1995, Aliveya_2018, Kimberland_1995). These data indicate that the variant is very likely to be associated with disease. In functional studies, the variant showed decreased protein expression and loss of interactions with transcription factors (Fauxman Bass, 2015). Kircher et al (Kircher_2018) also report reduced promoter activity for this variant. They speculate that this could be due to a known binding site for the erythroid Krppel factor (EKLF), a zinc-finger transcription factor in positions c.-142 to c.-136 that plays a critical role in erythropoiesis and regulation of beta-globin switching. The following publications have been ascertained in the context of this evaluation (PMID: 29893155, 26041423, 11857746, 8438884, 25910213, 18603555, 11857738, 12324499, 7599641, 31395865, 19103851, 7794779, 20704537). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003476899 SCV004219856 pathogenic not provided 2023-07-18 criteria provided, single submitter clinical testing The HBB c.-142C>T (also known -92C>T) variant is located in the promoter region of the HBB gene. It is described as mild promoter variant. Heterozygotes for this variant can be clinically asymptomatic, while compound heterozygous individuals for this variant and a Beta zero or severe Beta+ variant can develop thalassemia intermedia (PMID:7794779 (1995), 26041423 (2015), 26635043 (2016)).
OMIM RCV000016720 SCV000036990 pathogenic Beta-plus-thalassemia 1992-06-01 no assertion criteria provided literature only
GeneReviews RCV000445639 SCV000537287 not provided beta Thalassemia no assertion provided literature only

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