ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.93-15T>G (rs35456885)

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Total submissions: 3
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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
Integrated Genetics/Laboratory Corporation of America RCV000780335 SCV000917507 pathogenic Hemoglobinopathy 2017-12-28 criteria provided, single submitter clinical testing Variant summary: The HBB c.93-15T>G variant involves the alteration of a non-conserved intronic nucleotide in intron 1 and 3/5 splice prediction tools predict a significant impact on normal splicing. Functional analysis shows that this variant leads to splicing defect by resulting in the generation of an abnormal alternative acceptor splice site. Transient expression studies revealed a 4-fold decrease in the amount of RNA produced with > 99% of it being abnormally spliced (Metherall_1986). This variant is absent in 276752 control chromosomes (gnomAD). This variant was reported in BTHAL compound heterozygote and homozygote patients (Metherall_1986, Chouk_2004, and Jarjour_2014). It was reported in carrier screening studies (Tadmouri_1998, Boussiou_2008) and was considered to be a severe mutation. Multiple reputable databases classify this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
OMIM RCV000016713 SCV000036983 pathogenic beta^0^ Thalassemia 1986-10-01 no assertion criteria provided literature only

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