ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.93-15T>G

dbSNP: rs35456885
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665080 SCV000789141 likely pathogenic beta Thalassemia 2017-01-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000665080 SCV000917507 pathogenic beta Thalassemia 2022-11-02 criteria provided, single submitter clinical testing Variant summary: HBB c.93-15T>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 2/4 computational tools predict this variant creates cryptic 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing. Transient expression studies revealed a 4-fold decrease in the amount of RNA produced with > 99% of it being abnormally spliced (example: Metherall_1986). The variant was absent in 251042 control chromosomes (gnomAD). c.93-15T>G has been reported in the literature in multiple compound heterozygote and homozygote individuals affected with Beta Thalassemia (example: Metherall_1986, Chouk_2004 and Jarjour_2014). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV004568488 SCV005051817 pathogenic Beta-thalassemia HBB/LCRB 2024-02-01 criteria provided, single submitter curation
OMIM RCV000016713 SCV000036983 pathogenic Beta zero thalassemia 1986-10-01 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000665080 SCV001244511 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation
Natera, Inc. RCV000665080 SCV002089237 pathogenic beta Thalassemia 2017-03-17 no assertion criteria provided clinical testing

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