ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-80T>A (rs33980857)

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Total submissions: 7
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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 RCV000029962 SCV000052617 pathogenic beta Thalassemia 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508486 SCV000601320 pathogenic not provided 2017-04-20 criteria provided, single submitter clinical testing
Invitae RCV000508486 SCV000941728 likely pathogenic not provided 2020-09-02 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed to be homozygous or in combination with another HBB variant in individual(s) with beta thalassemia (PMID: 1487424, 1917531, 3382401, 20854126). 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 known as -30 T>A in the literature. ClinVar contains an entry for this variant (Variation ID: 15467). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of this non-coding change is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000147 SCV001156632 pathogenic not specified 2018-10-05 criteria provided, single submitter clinical testing The HBB c.-80T>A variant, also known as -30 (T>A), is published in the medical literature in individuals with beta thalassemia intermedia when in the homozygous state and in individuals with a deletion on the opposite chromosome (see link to HbVar database, Fei 1988, Griffon 2010). The variant is listed in the ClinVar database (Variation ID: 15467) and the dbSNP variant database (rs33980857). This variant occurs in the conserved promoter region (Giardine 2011) and is predicted to affect transcription factor binding , thus reducing but not completely abrogating the amount of message produced from that chromosome (beta +). Considering available information, this variant is classified as pathogenic. References: Link to variant in HbVar database: Fei YJ et al. Beta-thalassemia due to a T----A mutation within the ATA box. Biochem Biophys Res Commun. 1988 Jun 16;153(2):741-7. Giardine B et al. Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach. Nat Genet. 2011 Mar 20;43(4):295-301. Griffon C et al. Severe B-thalassemia intermedia in a compound heterozygous patient for the -30 (T>A) B(+)-thalassemia mutation and the D(0)B(+)-Senegalese deletion. Hemoglobin. 2010;34(5):505-8.
OMIM RCV000016725 SCV000036995 pathogenic Beta-plus-thalassemia 1992-01-01 no assertion criteria provided literature only
GeneReviews RCV000029962 SCV000537289 pathogenic beta Thalassemia 2015-05-14 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000029962 SCV001244528 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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