ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.316-7C>A (rs34483965)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667076 SCV000791471 likely pathogenic beta Thalassemia 2017-05-22 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000150 SCV001156635 likely pathogenic not specified 2018-09-27 criteria provided, single submitter clinical testing The c.[316-12T>C; 316-7C>A] complex variant is reported in the literature in multiple individuals as a very mild beta + thalassemia trait (Belisario 2015, Waye 2013), and has been found in trans with Hb S and Hb C in patients with clinical symptoms (Cross 2007, Belisario 2015, Waye 2013). The c.316-12T>C variant (rs755236703) is only observed on three alleles in the Genome Aggregation Database. The c.316-7C>A variant (rs34483965) is only observed on one allele in the Genome Aggregation Database. These are intronic variants in weakly conserved nucleotides, and computational analyses (Alamut v.2.11) predict that each variant may impact splicing by weakening the nearby canonical acceptor splice site, however, without mRNA analysis it is unclear how the combination of the two variants impact splicing. Based on available information, the c.[316-12T>C; 316-7C>A] complex variant is considered to be likely pathogenic. References: Belisario A et al. Very mild forms of Hb S/beta(+)-thalassemia in Brazilian children. Rev Bras Hematol Hemoter. 2015 37(3):198-201. Cross T et al. Sickle liver disease--an unusual presentation in a compound heterozygote for HbS and a novel beta-thalassemia mutation. Am J Hematol. 2007 82(9):852-4. Waye J et al. Mild beta(+)-thalassemia associated with two linked sequence variants: IVS-II-839 (T>C) and IVS-II-844 (C>A). Hemoglobin. 2013 37(4):378-86.
Baylor Genetics RCV001004563 SCV001163647 pathogenic Hb SS disease criteria provided, single submitter clinical testing

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