ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-79A>G (rs34598529)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000020326 SCV000677979 pathogenic beta Thalassemia 2017-06-16 criteria provided, single submitter clinical testing The -29A>G mutation is associated with beta thalassemia.
Fulgent Genetics,Fulgent Genetics RCV000763256 SCV000893893 pathogenic Beta-thalassemia, dominant inclusion body type; Fetal hemoglobin quantitative trait locus 1; Heinz body anemia; Hb SS disease; alpha Thalassemia; Susceptibility to malaria; beta Thalassemia; METHEMOGLOBINEMIA, BETA TYPE; Erythrocytosis 6, familial 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000020326 SCV000040702 pathogenic beta Thalassemia 2015-05-14 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000029961 SCV000052616 pathogenic Beta thalassemia intermedia 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000020326 SCV000697149 pathogenic beta Thalassemia 2016-04-26 criteria provided, single submitter clinical testing Variant summary: The c.-79A>G variant affects a conserved nucleotide in TATA box in 5'UTR. One in-silico tool predicts damaging outcome for this variant. This variant is found in 2/5008 control chromosomes at a frequency of 0.0003994, which does not exceed maximal expected frequency of a pathogenic allele (0.0111803). In functional studies the variant of interest was shown to reduce the production of the b-globin mRNA. This change is a widely accepted to be deleterious and multiple clinical laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Invitae RCV000810653 SCV000950878 pathogenic not provided 2018-12-12 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 is present in population databases (rs34598529, gnomAD 0.3%). This variant has been observed in several individuals and families affected with mild beta thalassemia (PMID: 2123063, 6583702, 3021607, 28385923, 2458145). This variant is also known as c.-29A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 15469). This sequence change, c.-79A>G, falls within the TATA box of the HBB gene and experimental studies have shown that this variant results in a reduction of B globin RNA compared to wild type HBB (PMID: 6583702). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000016727 SCV000036997 pathogenic Beta-plus-thalassemia 1986-10-01 no assertion criteria provided literature only

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