ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.316-70C>G (rs193922560)

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Total submissions: 4
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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 RCV001001830 SCV000052643 likely benign not specified 2021-05-25 criteria provided, single submitter clinical testing Variant summary: HBB c.316-70C>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 0.00076 in 31390 control chromosomes, predominantly at a frequency of 0.0028 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in HBB causing Hemoglobinopathy (0.00076 vs 0.011), allowing no conclusion about variant significance. c.316-70C>G has been reported in the literature. Normal hematological values were reportedly observed in two subjects heterozygous for the variant. Furthermore, the coinheritance of c.316-70C>G in trans with the classical b0-thal allele c.93-21G>A or Hb S in two individuals did not influence or change their typical hematological and clinical features as simple b-thal carrier and sickle cell anemia carrier, respectively (Vinciguerra_2016). Additionally, a recent paper reported 15 individuals who carried c.316-70C>G in a variety of combinations with other alpha-, beta- or delta-globin gene defects and they found no influence of this sequence variant on phenotype, ultimately concluding that it is benign without thalassemic effect (Grimholt_2018). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as likely benign, benign and pathogenic. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000874736 SCV001016956 benign not provided 2020-12-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282807 SCV001159510 likely benign none provided 2019-12-12 criteria provided, single submitter clinical testing
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000029988 SCV001244491 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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