ClinVar Miner

Submissions for variant NM_000518.4(HBB):c.23A>G (p.Glu8Gly) (rs34387455)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282306 SCV000883985 likely benign none provided 2020-07-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000756237 SCV000889366 uncertain significance not provided 2017-12-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781437 SCV000919457 likely benign not specified 2018-04-24 criteria provided, single submitter clinical testing Variant summary: HBB c.23A>G (p.Glu8Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 245938 control chromosomes (in gnomAD). This frequency is not higher than expected for a pathogenic variant in HBB causing Hemoglobinopathy (1.2e-05 vs 0.011), allowing no conclusion about variant significance. The variant, c.23A>G has been reported in the literature in a healthy individual in homozygosity (Brancati_1989) as well as in several healthy carriers (e.g. Smith_2016). The variant is known in the literature as a rare polymorphism that has been reported mostly in Southern Italian or of Mexican families (Lacerra 2002). Individuals, who have the variant of interest together with b-thal mutation are likely to have hematological values reflecting their b-thal carrier status. Studies of functional properties confirmed that the variant protein has normal oxygen affinity, cooperativity and Bohr effect with a slightly decreased stability that may have only a marginal role, considering that the variant is not associated with a clinically significant hemolytic process (Roth_1977, Lacerra_2002). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as Likely Benign.
OMIM RCV000016353 SCV000036621 other HEMOGLOBIN G (SAN JOSE) 2017-12-12 no assertion criteria provided literature only

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