ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.274C>T (p.Leu92=) (rs769583496)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507587 SCV000601265 uncertain significance not specified 2016-08-29 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756242 SCV000883992 uncertain significance not provided 2018-02-07 criteria provided, single submitter clinical testing The HBB c.274C>T; Leu91Leu variant (rs769583496) has been observed in Korean and Japanese individuals harboring a pathogenic allele (Park 2002, Wakamatsu 1994); it is not definitive whether these variants were confirmed to be in cis by molecular analyses, but they are reported as linked variants in the Japanese population. Erythrocyte indices (Hb, HbA2, HbF, MCV, MCH) in four individuals reported by Wakamatsu et al are most consistent with beta-thalassemia minor. This variant is reported in ClinVar (Variation ID: 439144) and is observed in the general population at a low overall frequency of 0.003% (7/246192 alleles, 6 alleles in East Asian population) in the Genome Aggregation Database. This is a synonymous change, the nucleotide is moderately conserved, and computational algorithms (SpliceSiteFinder-like, MaxEntScan, NNSplice, GeneSplicer, Human Splicing Finder) predict that this variant may impact splicing by strengthening a nearby cryptic donor site. However, given the lack of clinical and functional data, the significance of this variant on its own cannot be determined with certainty. References: Park S et al. Beta-thalassemia in the Korean population. Hemoglobin. 2002 May;26(2):135-45. Wakamatsu C et al. Molecular basis of beta-thalassemia in Japan: heterogeneity and origins of mutations. Acta Haematol. 1994;91(3):136-43.
Integrated Genetics/Laboratory Corporation of America RCV000507587 SCV000919465 likely benign not specified 2019-08-28 criteria provided, single submitter clinical testing

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