ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.273+4A>G (rs387906374)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV000007620 SCV001425430 uncertain significance Cystic fibrosis 2020-02-19 criteria provided, single submitter clinical testing This CFTR variant has been previously identified in patients with features of cystic fibrosis. It (rs397508734) is rare (<0.1%) in a large population dataset ( gnomAD: 5/281884 total alleles; 0.002%; no homozygotes). Bioinformatic analysis predicts that this variant may affect normal exon 3 splicing, although this has not been confirmed experimentally to our knowledge. We consider the clinical significance of c.273+4A>G to be uncertain at this time.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286598 SCV001473199 uncertain significance none provided 2019-08-01 criteria provided, single submitter clinical testing The CFTR c.273+4A>G variant (rs387906374), also known as 405+4A>G for traditional nomenclature, is reported in the literature in an individual with mild CF; however, a second variant was not identified in this individual (Ghanem 1994). This variant is also reported in the ClinVar database (Variation ID: 7199). Additionally, a nearby variant (c.273+3A>C) is considered to be CF-causing when found with an additional pathogenic variant (CFTR2 database). The c.273+4A>G variant is found in the general population with a low overall allele frequency of 0.002% (6/281884 alleles) in the Genome Aggregation Database. This is an intronic variant in a highly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. However, given the lack of clinical and functional data, the significance of the c.273+4A>G variant is uncertain at this time. REFERENCES CFTR2 database: https://cftr2.org/ Ghanem N et al. Identification of eight mutations and three sequence variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics. 1994 May 15;21(2):434-6.
OMIM RCV000007620 SCV000027821 pathogenic Cystic fibrosis 1994-05-15 no assertion criteria provided literature only

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