ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-142C>T (rs34883338)

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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 RCV000589915 SCV000697082 pathogenic Beta thalassemia intermedia 2019-10-14 criteria provided, single submitter clinical testing Variant summary: HBB c.-142C>T (aka -92C>T) is located in the untranscribed region upstream of the HBB gene region. The variant was absent in 31402 control chromosomes (gnomAD). c.-142C>T has been reported in the literature in individuals affected with Beta Thalassemia Intermedia (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. One other ClinVar submitter has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000016720 SCV000036990 pathogenic Beta-plus-thalassemia 1992-06-01 no assertion criteria provided literature only
GeneReviews RCV000445639 SCV000537287 pathogenic beta Thalassemia 2015-05-14 no assertion criteria provided literature only

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