Submissions for variant NM_000492.4(CFTR):c.1117-26_1117-25del

dbSNP: rs397508159

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811318	SCV001158230	benign	not provided	2019-11-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000577778	SCV001595156	likely benign	Cystic fibrosis	2024-05-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001811318	SCV005079038	uncertain significance	not provided	2023-08-16	criteria provided, single submitter	clinical testing	Identified in individuals with cystic fibrosis in published literature, but in whom limited clinical data was provided and a second CFTR variant was either not detected or not specified (Scotet et al., 2003; Raraigh et al., 2022); In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 34782259, 12815607)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005237476	SCV005885080	likely benign	not specified	2024-12-19	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.1117-26_1117-25delAT is located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.1e-05 in 241484 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1117-26_1117-25delAT has been reported in the literature in individuals affected with Cystic Fibrosis and Cystic Fibrosis screen positive with an inconclusive abstract diagnosis, without strong evidence for causality (Strom_2003, Dorfman_2010, Scotet_2003, Dorfman_2008, Raraigh_2021, Gonska_2021, Sickkids database). These report(s) do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 20059485, 18292811, 34814176, 34782259, 12815607, 12544470). ClinVar contains an entry for this variant (Variation ID: 53192). Based on the evidence outlined above, the variant was classified as likely benign.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577778	SCV000679078	not provided	Cystic fibrosis		no assertion provided	literature only