ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2988+1G>A (rs75096551)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
American College of Medical Genetics and Genomics (ACMG) RCV000007645 SCV000071402 pathogenic Cystic fibrosis 2004-03-03 practice guideline curation Converted during submission to Pathogenic.
CFTR2 RCV000007645 SCV000071456 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Invitae RCV000007645 SCV000074751 pathogenic Cystic fibrosis 2019-11-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 18 of the CFTR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs75096551, ExAC 0.09%). This variant is clearly defined as a cystic fibrosis (CF) causative allele (PMID: 23974870) and is included in the American College of Medical Genetics (ACMG) panel of CF variants (PMID: 15371902). It is also known as 3120+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 7224). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000759761 SCV000226734 pathogenic not provided 2016-12-27 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507554 SCV000603044 pathogenic not specified 2018-10-19 criteria provided, single submitter clinical testing The CFTR c.2988+1G>A variant (rs75096551), also known as 3120+1G>A, is reported in patients diagnosed with cystic fibrosis (Chavez-Saldana 2010, Masekela 2013, Wilschanski 1995), and is associated with elevated sweat levels and pancreatic insufficiency (Masekela 2013, Ooi 2012, Sosnay 2013, see CFTR2 database). Functional characterization indicates that exon 18 is skipped in the CFTR mRNA, and results in the absence of CFTR protein (Sharma 2014). This variant is reported as pathogenic in ClinVar (Variation ID: 7224), and found in the general population with an overall allele frequency of 0.01% (31/276728 alleles) in the Genome Aggregation Database. This variant abolishes the splice donor site and is predicted to alter splicing (Alamut v2.11). Based on available information, this variant is considered severely pathogenic. References: CFTR2 database link: https://cftr2.org/ Chavez-Saldana M et al. CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening. Rev Invest Clin. 2010; 62(6):546-52. Masekela R et al. Phenotypic expression of the 3120+1G>A mutation in non-Caucasian children with cystic fibrosis in South Africa. J Cyst Fibros. 2013; 12(4):363-6. Ooi C. et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012; 11(5):355-62. Sharma N et al. Experimental assessment of splicing variants using expression minigenes and comparison with in silico predictions. Hum Mutat. 2014; 35(10):1249-59. Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013; 45(10):1160-7. Wilschanski M et al. Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations. J Pediatr. 1995; 127(5):705-10.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000007645 SCV000784252 pathogenic Cystic fibrosis 2018-03-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759761 SCV000889304 pathogenic not provided 2015-11-04 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000007645 SCV000891677 pathogenic Cystic fibrosis 2017-12-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763580 SCV000894419 pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000007645 SCV001137489 pathogenic Cystic fibrosis 2019-05-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004285 SCV001163161 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000007645 SCV001169503 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Myriad Women's Health, Inc. RCV000007645 SCV001194076 pathogenic Cystic fibrosis 2019-11-12 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.2988+1G>A(aka 3120+1G>A) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID 23974870. Classification of NM_000492.3(CFTR):c.2988+1G>A(aka 3120+1G>A) is based on the following criteria: The variant is located at a canonical splice site, is expected to disrupt gene function and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
OMIM RCV000007645 SCV000027846 pathogenic Cystic fibrosis 1998-08-01 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000007645 SCV000052162 pathogenic Cystic fibrosis 2015-06-22 no assertion criteria provided clinical testing
Natera Inc RCV001027899 SCV001190622 pathogenic CFTR-related disorders 2019-05-20 no assertion criteria provided clinical testing

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