ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-31C>T (rs63750628)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000029956 SCV000052611 uncertain beta Thalassemia 2011-08-18 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000507019 SCV000603911 likely benign not specified 2018-08-02 criteria provided, single submitter clinical testing The HBB c.-31C>T variant (rs63750628), also known as +20 C>T, is reported in patients with beta-thalassemia, but found in-cis with the pathogenic c.316-106C>G variant, also known as IVS-II-745 (C>G) (Orkin 1982, Ropero 2013, HbVar database). This variant is reported in ClinVar (Variation ID: 36291), and found in the general European population with an allele frequency of 0.01% (15/111138 alleles) in the Genome Aggregation Database. The variant is located in the 5' untranslated region at a nucleotide that is weakly conserved, and computational analyses (Mutation Taster, NetStart 1.0) predict that this variant has no impact on translation initiation. Based on the available information, this variant is considered to be likely benign. References: Link to HbVar for +20 (C>T): http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=2509 Orkin S et al. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982; 296(5858):627-31. Ropero P et al. Association in cis of the mutations +20 (C>T) in the 5' untranslated region and IVS-II-745 (C>G) on the beta-globin gene. Hemoglobin. 2013; 37(2):112-8.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000755548 SCV000888153 uncertain significance not provided 2018-09-11 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029956 SCV000914521 uncertain significance beta Thalassemia 2018-12-05 criteria provided, single submitter clinical testing The HBB c.-31C>T variant, commonly referred to as 5’UTR+20, C>T, has been described in at least four studies in which it is found in cis with the same intronic variant, c.316-106C>G (commonly referred to as IVS-II-745 (C>G)). The c.-31C>T variant was found in a homozygous state in three individuals with a severe form of beta-thalassemia, in a compound heterozygous state in an additional three individuals with the same severe phenotype, and in a heterozygous state in six individuals, all with a milder phenotype. In all cases, the c.-31C>T variant was in cis with the intronic variant (Yavarian et al. 2001; Liaw et al. 2009; Ropero et al. 2013; Farashi et al. 2015). Sirdah et al. (2013) also reported the c.-31C>T variant in a compound heterozygous state in one individual with beta-thalassemia who did not carry the intronic variant. The c.-31C>T variant is reported at a frequency of 0.00014 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the c.-31C>T variant is classified as a variant of unknown significance for HBB-related disorders.
Illumina Clinical Services Laboratory,Illumina RCV001104361 SCV001261218 benign Hb SS disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001104362 SCV001261220 uncertain significance Fetal hemoglobin quantitative trait locus 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001104363 SCV001261221 benign Hemoglobin E 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000029956 SCV001244457 benign beta Thalassemia 2019-11-25 no assertion criteria provided curation

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