ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.3285A>T (p.Thr1095=)

gnomAD frequency: 0.00570  dbSNP: rs1800118
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Total submissions: 21
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000215556 SCV000227628 benign not specified 2015-12-21 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000215556 SCV000268872 benign not specified 2013-02-21 criteria provided, single submitter clinical testing Thr1095Thr in exon 20 of CFTR: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.7% (57/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs1800118).
Invitae RCV000232081 SCV000285003 benign Cystic fibrosis 2024-01-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV001095258 SCV000304488 likely benign CFTR-related disorder 2023-03-01 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Illumina Laboratory Services, Illumina RCV001095258 SCV000466522 uncertain significance CFTR-related disorder 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000586681 SCV000603000 benign not provided 2023-11-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586681 SCV000696963 benign not provided 2017-05-04 criteria provided, single submitter clinical testing Variant summary: This silent variant CFTR c.3285A>T (p.Thr1095Thr), alternatively known as 3417A>T, is located at a non-conserved position in exon 20 of CFTR and it is 82 nucleotides upstream to the nearest exon-intron junction. The variant is not predicted to impact splicing by 5/5 splice prediction tools. ESEfinder predicts the loss of a SC35 binding motif and Mutation Taster predicts as disease-causing. However, predictions from in silico tools are not definitive. There are no experimental in vitro or in vivo functional studies reported for the variant at this time. It has been observed in patients with infertility (non-obstructive infertility, oligoasthenoteratozoospermia and oligoasthenoteratozoospermia), pancreatitis, sarcoidosis, bronchiectasis and COPD. While CFTR mutations may represent a risk factor for these phenotypes, there is a lack of conclusive evidence. Multiple studies have reported this variant to occur in controls and patients at similar frequencies, suggesting that this variant is unlikely to be a risk allele. There are two reports in which this variant was found with CFin 1 German family and in 1 patient referred to CF testing. However, in both studies, cosegregation and/or co-occurrence information is not provided and authors refer to this variant as a polymorphism. This variant was found in 590/124728 control chromosomes (2 homozygotes) including ExAC at an allele frequency of 0.0047303, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This population frequency supports benign outcome for phenotypes other than CF and CBAVD. Most publications spanning over a decade (1994-2009) report this variant as a polymorphism (Ravnik-Glavac 2001, Gallati 2009, Dork 1994, Tzetis 2001, Shackelton 1994). Multiple clinical laboratories/reputable database have classified this variant as likely benign/benign. Taken together, this variant is classified as 'Benign'.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586681 SCV000888083 benign not provided 2021-02-19 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000586681 SCV001155241 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing CFTR: BP4, BP7, BS2
Johns Hopkins Genomics, Johns Hopkins University RCV000232081 SCV001167223 benign Cystic fibrosis 2019-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000232081 SCV001181052 likely benign Cystic fibrosis 2015-01-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab RCV000232081 SCV001653481 likely benign Cystic fibrosis 2021-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000586681 SCV001785783 likely benign not provided 2020-09-21 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 16251901, 23378595, 7515303, 15536480, 7525450, 16128988, 11354633, 11788091, 10601093)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000232081 SCV002507397 likely benign Cystic fibrosis 2020-03-05 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002257477 SCV002529713 likely benign Hereditary pancreatitis 2021-04-13 criteria provided, single submitter curation
Institute of Human Genetics, University of Leipzig Medical Center RCV000232081 SCV002574032 likely benign Cystic fibrosis 2022-09-05 criteria provided, single submitter curation This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: BS2, BP4, BP7
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000215556 SCV001955246 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000586681 SCV001975581 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000586681 SCV002036061 likely benign not provided no assertion criteria provided clinical testing
Natera, Inc. RCV001095258 SCV002083624 likely benign CFTR-related disorder 2017-03-28 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001095258 SCV002507481 likely benign CFTR-related disorder 2020-03-05 no assertion criteria provided clinical testing

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