ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.3285A>T (p.Thr1095=) (rs1800118)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000215556 SCV000227628 benign not specified 2015-12-21 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare 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 (; dbSNP rs1800118).
Invitae RCV000232081 SCV000285003 benign Cystic fibrosis 2020-12-05 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000215556 SCV000304488 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001095258 SCV000466522 uncertain significance CFTR-related disorders 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 RCV001282724 SCV000603000 benign none provided 2020-05-29 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 2016-08-04 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586681 SCV001155241 likely benign not provided 2020-02-01 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000232081 SCV001167223 benign Cystic fibrosis 2019-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV001019665 SCV001181052 likely benign Inborn genetic diseases 2015-01-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Nilou-Genome Lab RCV000232081 SCV001653481 likely benign Cystic fibrosis 2021-05-18 criteria provided, single submitter clinical testing

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