ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-78A>G (rs33931746)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000029960 SCV000052615 pathogenic beta Thalassemia 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506257 SCV000601318 pathogenic not provided 2017-04-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000122 SCV001156561 pathogenic not specified 2018-08-24 criteria provided, single submitter clinical testing The HBB c.-78A>G variant (commonly known as -28 (A->G)) is a common beta+ thalassemia variant found in Asian populations (see HbVar link, Yamsri 2011), and has been reported in an individual with beta thalassemia who was homozygous for the variant (Orkin 1983). In addition, functional characterization of the variant indicates a 3-5 fold reduction of beta globin mRNA (Orkin 1983). This variant is listed in the dbSNP database (rs33931746), and is not observed in the general population (1000 Genomes Project). The c.-78A>G variant is located in a conserved region of the beta globin gene promoter and is considered to be pathogenic. REFERENCES Link to HbVar database for -28 (A->G): http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=769 Orkin SH et al. ATA box transcription mutation in beta-thalassemia. Nucleic Acids Res. 1983 Jul 25;11(14):4727-34. Yamsri S et al. Genotype and phenotype characterizations in a large cohort of beta-thalassemia heterozygote with different forms of alpha-thalassemia in northeast Thailand. Blood Cells Mol Dis. 2011 Aug 15;47(2):120-4.
Baylor Genetics RCV001004362 SCV001163300 pathogenic Hb SS disease criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000029960 SCV001193862 likely pathogenic beta Thalassemia 2019-12-09 criteria provided, single submitter clinical testing NM_000518.4(HBB):c.-78A>G(aka -28A>G) is classified as likely pathogenic in the context of Hb beta chain-related hemoglobinopathy and is a beta-plus variant associated with beta thalessemia. Sources cited for classification include the following: PMID 8435318, 9160698 and 6308558. Classification of NM_000518.4(HBB):c.-78A>G(aka -28A>G) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000506257 SCV001224372 pathogenic not provided 2019-12-27 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 not present in population databases (ExAC no frequency). This variant has been observed in individuals with beta thalassemia (PMID: 2014803, 28385923, 8435318, 20035706). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as -28A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 15471). This variant has been reported to affect HBB expression (PMID: 6308558). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000016729 SCV000036999 pathogenic Beta-plus-thalassemia 1983-07-25 no assertion criteria provided literature only
GeneReviews RCV000029960 SCV000040701 pathogenic beta Thalassemia 2015-05-14 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000029960 SCV001244522 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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