ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.316-125A>G (rs63751175)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281704 SCV000601277 benign not specified 2020-02-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001281704 SCV000697109 likely benign not specified 2021-06-04 criteria provided, single submitter clinical testing Variant summary: HBB c.316-125A>G is located at a position not widely known to affect splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00016 in 31394 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.316-125A>G, has been reported in the literature in a homozygous patient from a consanguineous family presenting with BTHAL-ITMD (Agouti_2007). However, recent studies identified this variant in heterozygosity in multiple individuals with normal hematological and electrophoretic features, in a healthy alpha-thalassemia carrier together with an alpha deletion, in a healthy beta-thalassemia carrier in compound heterozygosity with HBB c.93+1G>A (Vinciguerra_2017, Grimholt_2018), and in a healthy individual in compound heterozygosity with the pathogenic HBB c.364G>C (Hb D-Punjab). All studies classified the variant as a polymorphism due to the carriers having the expected phenotypes given their genotypes. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have 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.
Invitae RCV000508509 SCV001001439 likely benign not provided 2020-12-02 criteria provided, single submitter clinical testing
GeneDx RCV000508509 SCV001785786 likely benign not provided 2019-06-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30047296, 21423179, 18976160, 27258795, 24401016, 17994377, 29171316)
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV001078266 SCV001244411 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation
Natera, Inc. RCV001078266 SCV001463832 likely benign beta Thalassemia 2020-09-16 no assertion criteria provided clinical testing

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