Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000492.4(CFTR):c.4056G>T (p.Gln1352His)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Pathogenic(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: May 26, 2021)
Last evaluated:
Nov 3, 2020
Accession:
VCV000035882.9
Variation ID:
35882
Description:
single nucleotide variant
Help

NM_000492.4(CFTR):c.4056G>T (p.Gln1352His)

Allele ID
44546
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q31.2
Genomic location
7: 117664780 (GRCh38) GRCh38 UCSC
7: 117304834 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.117304834G>T
NM_000492.3:c.4056G>T NP_000483.3:p.Gln1352His missense
LRG_663:g.203997G>T
... more HGVS
Protein change
Q1352H
Other names
-
Canonical SPDI
NC_000007.14:117664779:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00419 (C)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA260248
dbSNP: rs113857788
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Apr 10, 2020 RCV000757090.4
Uncertain significance 1 criteria provided, single submitter Nov 3, 2020 RCV000029537.2
Likely benign 1 criteria provided, single submitter Sep 7, 2020 RCV000808411.3
Pathogenic 1 criteria provided, single submitter Jan 23, 2020 RCV001282161.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CFTR - - GRCh38
GRCh37
1974 2730

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jan 23, 2020)
criteria provided, single submitter
Method: clinical testing
none provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885195.2
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The CFTR c.4056G>T; p.Gln1352His variant (rs113857788), and another variant resulting in the same amino acid change (c.4056G>C; p.Gln1352His), are reported in the literature in multiple … (more)
Uncertain significance
(Apr 10, 2020)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713444.1
Submitted: (May 26, 2021)
Evidence details
Uncertain significance
(May 11, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888094.1
Submitted: (Aug 31, 2018)
Evidence details
Uncertain significance
(Nov 03, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052189.2
Submitted: (Dec 02, 2020)
Evidence details
Publications
PubMed (38)
Comment:
Variant summary: CFTR c.4056G>T (p.Gln1352His) results in a non-conservative amino acid change located in the ABC transporter-like domain of the encoded protein sequence. Five of … (more)
Likely benign
(Sep 07, 2020)
criteria provided, single submitter
Method: clinical testing
Cystic fibrosis
Allele origin: germline
Invitae
Accession: SCV000948520.3
Submitted: (Jan 07, 2021)
Evidence details

Functional evidence

Help
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Help
Title Author Journal Year Link
Genetics of the congenital absence of the vas deferens. Bieth E Human genetics 2021 PMID: 32025909
The Cystic Fibrosis Transmembrane Conductance Regulator 470 Met Allele Is Associated with an Increased Risk of Chronic Pancreatitis in Both Asian and Caucasian Populations: A Meta-Analysis. Zhou D Genetic testing and molecular biomarkers 2020 PMID: 31940241
Determining the pathogenicity of CFTR missense variants: Multiple comparisons of in silico predictors and variant annotation databases. Michels M Genetics and molecular biology 2019 PMID: 31808782
Functional Assays Are Essential for Interpretation of Missense Variants Associated with Variable Expressivity. Raraigh KS American journal of human genetics 2018 PMID: 29805046
Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling. de Souza DAS Andrology 2018 PMID: 29216686
CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants. Claustres M Human mutation 2017 PMID: 28603918
CFTR gene mutations and polymorphism are associated with non-obstructive azoospermia: From case-control study. Jiang L Gene 2017 PMID: 28456595
PRSS1, SPINK1, CFTR, and CTRC Pathogenic Variants in Korean Patients With Idiopathic Pancreatitis. Cho SM Annals of laboratory medicine 2016 PMID: 27578509
Risk of asthma in heterozygous carriers for cystic fibrosis: A meta-analysis. Nielsen AO Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2016 PMID: 27324553
The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing. Schrijver I The Journal of molecular diagnostics : JMD 2016 PMID: 26708955
Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk. Lim RM Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 25880441
Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations. Ramalho AS Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2016 PMID: 25735457
Targeted next-generation sequencing effectively analyzed the cystic fibrosis transmembrane conductance regulator gene in pancreatitis. Nakano E Digestive diseases and sciences 2015 PMID: 25492507
Does integration of various ion channel measurements improve diagnostic performance in cystic fibrosis? Ooi CY Annals of the American Thoracic Society 2014 PMID: 24697796
Association of CFTR gene mutation with bronchial asthma. Maurya N The Indian journal of medical research 2012 PMID: 22664493
Association of CFTR gene mutation with bronchial asthma and its severity in Indian children: a case-control study. Awasthi S Annals of human biology 2012 PMID: 22324837
Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Steiner B Human mutation 2011 PMID: 21520337
Cystic fibrosis conductance regulator, tumor necrosis factor, interferon alpha-10, interferon alpha-17, and interferon gamma genotyping as potential risk markers in pulmonary sarcoidosis pathogenesis in Greek patients. Makrythanasis P Genetic testing and molecular biomarkers 2010 PMID: 20722470
A Japanese adult case of forme fruste cystic fibrosis. Oka H Internal medicine (Tokyo, Japan) 2010 PMID: 20558957
The L441P mutation of cystic fibrosis transmembrane conductance regulator and its molecular pathogenic mechanisms in a Korean patient with cystic fibrosis. Gee HY Journal of Korean medical science 2010 PMID: 20052366
Independent contribution of common CFTR variants to chronic pancreatitis. de Cid R Pancreas 2010 PMID: 19812525
Cystic fibrosis transmembrane conductance regulator mutations in azoospermic and oligospermic men and their partners. Gallati S Reproductive biomedicine online 2009 PMID: 20021716
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation associated with a congenital bilateral absence of vas deferens. Sakamoto H International journal of urology : official journal of the Japanese Urological Association 2008 PMID: 18304229
Primary sclerosing cholangitis in childhood is associated with abnormalities in cystic fibrosis-mediated chloride channel function. Pall H The Journal of pediatrics 2007 PMID: 17719933
Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling. Ratbi I Human reproduction (Oxford, England) 2007 PMID: 17329263
Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. Keiles S Pancreas 2006 PMID: 17003641
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asians with chronic pulmonary disease: a pilot study. Ngiam NS Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2006 PMID: 16678503
Detection of F508del mutation in cystic fibrosis transmembrane conductance regulator gene mutation among Malays. Zilfalil BA Singapore medical journal 2006 PMID: 16435054
Spectrum of CFTR mutations on Réunion Island: impact on neonatal screening. Bienvenu T Human biology 2005 PMID: 16596947
Gene SNPs and mutations in clinical genetic testing: haplotype-based testing and analysis. Lee JE Mutation research 2005 PMID: 15829248
Cystic fibrosis in Korean children:a case report identified by a quantitative pilocarpine iontophoresis sweat test and genetic analysis. Ahn KM Journal of Korean medical science 2005 PMID: 15716623
Molecular pathology of the CFTR locus in male infertility. Claustres M Reproductive biomedicine online 2005 PMID: 15705292
Do CFTR gene polymorphisms determine the susceptibility to alcoholic chronic pancreatitis? Naruse S Internal medicine (Tokyo, Japan) 2004 PMID: 15645635
Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis. Fujiki K Journal of medical genetics 2004 PMID: 15121783
Improved detection of cystic fibrosis mutations in infertility patients with DNA sequence analysis. Danziger KL Human reproduction (Oxford, England) 2004 PMID: 14998948
A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. Lee JH Human molecular genetics 2003 PMID: 12952861
Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens. Dörk T Human genetics 1997 PMID: 9272157
Mutations in the cystic fibrosis gene in men with congenital bilateral absence of the vas deferens. De Braekeleer M Molecular human reproduction 1996 PMID: 9239681

Text-mined citations for rs113857788...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 11, 2021