Submissions for variant NM_000492.4(CFTR):c.3964-3C>G

dbSNP: rs397508652

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR-France	RCV000577488	SCV001169379	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Baylor Genetics	RCV003474597	SCV004213532	likely pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-04-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000577488	SCV005077091	pathogenic	Cystic fibrosis	2024-04-30	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.3964-3C>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes the canonical 3' acceptor site. Two predict the variant weakens the canonical 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing by skipping exon 24 (Raynal_2013). The variant was absent in 251058 control chromosomes. c.3964-3C>G has been reported in the literature in at-least two individuals affected with Cystic Fibrosis (example, Raynal_2013, Lakeman_2008). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 18373402, 23381846). ClinVar contains an entry for this variant (Variation ID: 53864). Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577488	SCV000679393	not provided	Cystic fibrosis		no assertion provided	literature only