ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.92+5G>A (rs33915217)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000030004 SCV000052659 pathogenic beta Thalassemia 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Counsyl RCV000030004 SCV000220579 likely pathogenic beta Thalassemia 2014-08-06 criteria provided, single submitter literature only
Invitae RCV001216321 SCV001388112 pathogenic not provided 2019-04-19 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the HBB gene. It does not directly change the encoded amino acid sequence of the HBB protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another HBB variant in multiple individuals affected with beta thalassemia (PMID: 3021139, 2200760, 10815781, 28366028, 23590658, 1917531). This variant is also known as IVS-1-5 (G>A) or IVS-I-5 in the literature. ClinVar contains an entry for this variant (Variation ID: 15449). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 3671081). A different variant affecting this nucleotide (c.92+5G>C) has been determined to be pathogenic (PMID: 27263053, 23162295, 22392582, 19000664, 18294253, 6188062). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000016707 SCV000036977 pathogenic Beta-plus-thalassemia 1986-09-14 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000030004 SCV001244505 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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