ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3485G>A (p.Arg1162Gln)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.3485G>A (p.Arg1162Gln)
Variation ID: 555228 Accession: VCV000555228.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117627538 (GRCh38) [ NCBI UCSC ] 7: 117267592 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 5, 2018 May 1, 2024 Feb 9, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3485G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Arg1162Gln missense NC_000007.14:g.117627538G>A NC_000007.13:g.117267592G>A NG_016465.4:g.166755G>A LRG_663:g.166755G>A LRG_663t1:c.3485G>A LRG_663p1:p.Arg1162Gln - Protein change
- R1162Q
- Other names
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- Canonical SPDI
- NC_000007.14:117627537:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00080 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00017
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CFTR | - | - |
GRCh38 GRCh37 |
3689 | 5008 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
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Sep 13, 2023 | RCV000671007.10 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Mar 27, 2023 | RCV000732689.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 9, 2024 | RCV002265847.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 14, 2022 | RCV002507173.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Dec 04, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000795942.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Uncertain significance
(Apr 03, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000860669.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Jan 14, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888086.2
First in ClinVar: Dec 16, 2018 Last updated: Jan 26, 2021 |
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Uncertain significance
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002027505.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Uncertain significance
(Feb 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pancreatitis
Bronchiectasis with or without elevated sweat chloride 1 Cystic fibrosis Congenital bilateral aplasia of vas deferens from CFTR mutation
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002815698.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Sep 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003796652.2
First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1162 of the CFTR protein (p.Arg1162Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1162 of the CFTR protein (p.Arg1162Gln). This variant is present in population databases (rs1800120, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of cystic fibrosis and/or cystic fibrosis (PMID: 11788090, 30938940, 32026723). ClinVar contains an entry for this variant (Variation ID: 555228). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Mar 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV004039790.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
Observed in individuals with features of cystic fibrosis who also harbored second CFTR variants, but familial segregation and additional clinical information was not provided (Banjar … (more)
Observed in individuals with features of cystic fibrosis who also harbored second CFTR variants, but familial segregation and additional clinical information was not provided (Banjar et al., 2020); Observed in an individual with alcohol-related pancreatitis and an individual with frequent pneumonias, pancreatic sufficiency, and a normal sweat chloride test (Monaghan et al., 2000; Strandvik et al., 2001); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 23974870, 25033378, 32292813, 34996830, 30938940, 10982968, 32026723, 11788090) (less)
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Uncertain significance
(Jul 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003831636.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Sep 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV004239076.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
CFTR c.3485G>A has been identified as a single heterozygous variant in two individuals with features of cystic fibrosis, but not a classic cystic fibrosis phenotype. … (more)
CFTR c.3485G>A has been identified as a single heterozygous variant in two individuals with features of cystic fibrosis, but not a classic cystic fibrosis phenotype. This CFTR variant (rs1800120) is rare (<0.1%) in a large population dataset (gnomADv2.1.1: 25/282012 total alleles; 0.009%; no homozygotes) and has been reported in ClinVar (Variation ID: 555228). Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the second predicts that it would be tolerated. The arginine residue at this position is evolutionarily conserved across all species assessed. We consider the clinical significance of CFTR c.3485G>A to be uncertain at this time. (less)
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Uncertain significance
(Feb 09, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002548060.3
First in ClinVar: Jul 18, 2022 Last updated: Apr 15, 2024 |
Comment:
Variant summary: CFTR c.3485G>A (p.Arg1162Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging … (more)
Variant summary: CFTR c.3485G>A (p.Arg1162Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.8e-05 in 250616 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in CFTR causing Cystic Fibrosis (8.8e-05 vs 0.013), allowing no conclusion about variant significance. c.3485G>A has been reported in the literature in individuals affected with Cystic Fibrosis and pancreatitis, without strong evidence for causality (example: Strandvik_2001, Monaghan_2000, Atag_2019, Benjar_2020, Benjar_2020). These reports do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30938940, 32026723, 32292813, 10982968, 11788090). ClinVar contains an entry for this variant (Variation ID: 555228). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Feb 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002617621.3
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.R1162Q variant (also known as c.3485G>A), located in coding exon 22 of the CFTR gene, results from a G to A substitution at nucleotide … (more)
The p.R1162Q variant (also known as c.3485G>A), located in coding exon 22 of the CFTR gene, results from a G to A substitution at nucleotide position 3485. The arginine at codon 1162 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in one individual with frequent pneumonia who had normal pancreatic function and sweat chloride levels; this individual did not have a second CFTR alteration (Strandvik B et al. Genet. Test., 2001;5:235-42). R1162 is located at the hinge region of the CFTR protein and may also act as an anchor (LaRusch J et al. PLoS Genet., 2014 Jul;10:e1004376). However, functional studies of a different variant at the same position (p.R1162L) demonstrated normal CFTR protein processing and chloride conductance (Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7). This amino acid position is highly conserved in available vertebrate species. In addition, p.R1162Q is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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The prevalence of viral infections in children with cystic fibrosis in a tertiary care center in Saudi Arabia. | Banjar H | International journal of pediatrics & adolescent medicine | 2020 | PMID: 32292813 |
Genotype patterns for mutations of the cystic fibrosis transmembrane conductance regulator gene: a retrospective descriptive study from Saudi Arabia. | Banjar HH | Annals of Saudi medicine | 2020 | PMID: 32026723 |
Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul. | Atag E | Pediatric pulmonology | 2019 | PMID: 30938940 |
Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis. | LaRusch J | PLoS genetics | 2014 | PMID: 25033378 |
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
Spectrum of mutations in the CFTR gene of patients with classical and atypical forms of cystic fibrosis from southwestern Sweden: identification of 12 novel mutations. | Strandvik B | Genetic testing | 2001 | PMID: 11788090 |
Mutation analysis of the cystic fibrosis and cationic trypsinogen genes in patients with alcohol-related pancreatitis. | Monaghan KG | American journal of medical genetics | 2000 | PMID: 10982968 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR | - | - | - | - |
Text-mined citations for rs1800120 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.