ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.4242+13A>G (rs76179227)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000079005 SCV000110874 benign not specified 2013-04-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000079005 SCV000270059 benign not specified 2017-07-31 criteria provided, single submitter clinical testing c.4242+13A>G in intron 26 of CFTR: This variant is not expected to have clinical significance because it has been identified in 1.6% (159/10116) of Ashkenazi Je wish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broa; dbSNP rs76179227). It was also identified in 5 homozygotes in gn omAD.
Invitae RCV000987967 SCV000285006 benign Cystic fibrosis 2020-12-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000079005 SCV000304496 likely benign not specified criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282800 SCV000603039 benign none provided 2020-08-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587429 SCV000697015 benign not provided 2016-06-28 criteria provided, single submitter clinical testing Variant summary: The CFTR c.4242+13A>G variant involves the alteration of a non-conserved intronic nucleotide at a position not widely known to affect normal splicing. One in silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict the variant not to affect splicing, and this prediction is supported by a minigene splicing assay showing no abnormal RNA products from a minigene containing this intronic variant. This variant was found in 424/120694 control chromosomes (including 1 homozygote), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0051196 (333/65044). This frequency is less than the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603), and it cannot be ruled out that the homozygote could be affected since the ExAC cohort is a general population cohort rather than a healthy or disease-free cohort. Although this variant is found at a frequency less than the most common pathogenic CFTR variant, DeltaF508 (allele frequency in ExAC of 823/121296), c.4242+13A>G is found at a frequency greater than 2-fold higher than the second most common pathogenic CFTR variant in ExAC, c.350G>A (p.Arg117His; 185/120360), highly suggesting that c.4242+13A>G is not pathogenic.Although the variant has been found in patients reported in the literature, there are no reports that show the variants clear-cut causal role in CF and/or CBAVD. In other CFTR-RD phenotypes (asthma, DB, and COPD), this variant was observed at similar frequencies in cases and controls, supporting the notion that it is not a risk factor for these milder phenotypes either. To our knowledge, there was only one report of the variant co-occurring with a pathogenic variant, c.5T_TG11, in a diffuse bronchiectasis patient; however, c.-1043dupT (not in ClinVar and not yet internally classified) was also identified in this patient, phase of these variants was not specified, segregation studies were not performed, and authors consider the variant of interest to be a polymorphism since functional studies showed no effect on splicing (Bergougnoux_JCF_2015). Additionally, UMD reports the variant as a complex allele with c.2538G>A (p.Trp846X) and c.1521_1523delCTT (p.Phe508del) on the other allele in an individual with CF (unpublished reference), suggesting that the variant of interest is not causative in this patient. Furthermore, multiple papers as well as Emory Genetics lab via ClinVar and SickKids report the variant as a benign polymorphism. Taken together, this intronic CFTR variant has been classified as Benign.
Mendelics RCV000987967 SCV001137500 benign Cystic fibrosis 2019-05-28 criteria provided, single submitter clinical testing
CFTR-France RCV000987967 SCV001169177 benign Cystic fibrosis 2018-01-29 criteria provided, single submitter curation the variant does not result in CFTR-RD neither
Illumina Clinical Services Laboratory,Illumina RCV001160217 SCV001322000 benign CFTR-related disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Natera, Inc. RCV000987967 SCV001456318 benign Cystic fibrosis 2020-09-16 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000079005 SCV001926317 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.