ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3897A>G (p.Thr1299=)
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.
Uncertain significance(1); Benign(5); Likely benign(7)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.3897A>G (p.Thr1299=)
Variation ID: 93154 Accession: VCV000093154.70
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117652865 (GRCh38) [ NCBI UCSC ] 7: 117292919 (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 Oct 2, 2016 Jul 15, 2024 Apr 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3897A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Thr1299= synonymous NC_000007.14:g.117652865A>G NC_000007.13:g.117292919A>G NG_016465.4:g.192082A>G LRG_663:g.192082A>G LRG_663t1:c.3897A>G LRG_663p1:p.Thr1299= - Protein change
- Other names
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- Canonical SPDI
- NC_000007.14:117652864:A:G
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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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0.00040 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00040
1000 Genomes Project 30x 0.00047
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00085
The Genome Aggregation Database (gnomAD) 0.00101
The Genome Aggregation Database (gnomAD), exomes 0.00104
Exome Aggregation Consortium (ExAC) 0.00114
Trans-Omics for Precision Medicine (TOPMed) 0.00117
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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 |
3736 | 5066 |
Conditions - Germline
Condition
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Feb 2, 2022 | RCV000150339.27 | |
Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
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Apr 1, 2024 | RCV000590053.44 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV001007581.20 | |
CFTR-related disorder
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Uncertain significance (3) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001158876.15 |
Likely benign (1) |
criteria provided, single submitter
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Apr 21, 2021 | RCV002257405.8 |
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
Help
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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Likely benign
(-)
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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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PreventionGenetics, part of Exact Sciences
Accession: SCV000304495.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(Jan 11, 2017)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000110872.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 10
Sex: mixed
|
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Likely benign
(Feb 21, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000197442.4
First in ClinVar: Jan 30, 2015 Last updated: Dec 06, 2016 |
Comment:
Thr1299Thr in exon 24 of CFTR: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue … (more)
Thr1299Thr in exon 24 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 0.1% (10/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs1800131). (less)
Number of individuals with the variant: 1
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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CFTR-Related Disorders
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001320539.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Likely benign
(Apr 21, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary pancreatitis
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002529721.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888092.3
First in ClinVar: Feb 17, 2019 Last updated: Dec 31, 2022 |
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Benign
(Jan 31, 2024)
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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: SCV000260695.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
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Benign
(Nov 16, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602975.8
First in ClinVar: Dec 06, 2016 Last updated: Feb 20, 2024 |
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Benign
(Oct 24, 2016)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696999.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The CFTR c.3897A>G (p.Thr1299Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a … (more)
Variant summary: The CFTR c.3897A>G (p.Thr1299Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 141/121634 control chromosomes (1 homozygote) at a frequency of 0.0011592, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603), however the homozygous occurrence does suggest a benign role of the variant. In the literature, the variant is reported in both control and patient populations across multiple ethnicities. However, genotypic information of the patients carrying the variant is not clearly specified in publications, and most of them classify it as a 'polymorphism.' One LabCorp specimen carries F508del (DV) and c.1021T>C (DV) (phase of the variants unknown) and the clinical representation of the pt is reported to be CF. In addition, UMD classifies the variant as a polymorphism that is reported in 5 patients (CF or CBAVD), each carrying two other deleterious variants. Although phase of the two deleterious variants is not reported for every patient, UMD cites 2 CF patients that carry p.Lys710X in cis with p.Thr1299Thr. Thus, we have a unequivocal evidence of the presence of deleterious variant(s) in cis with this silent variant in CF patients, suggesting a notion that it is not causally related to these phenotypes and is likely to be a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as benign. (less)
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Likely benign
(Jul 06, 2019)
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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: SCV001167216.1
First in ClinVar: Mar 08, 2020 Last updated: Mar 08, 2020 |
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Benign
(Jan 29, 2018)
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criteria provided, single submitter
Method: curation
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cystic fibrosis
Affected status: yes, no
Allele origin:
germline
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CFTR-France
Accession: SCV001169180.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Comment:
the variant does not result in CFTR-RD neither
Observation 1: Observation 2: |
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Likely benign
(May 23, 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: SCV001182989.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
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 … (more)
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. (less)
|
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Likely benign
(Apr 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001501422.20
First in ClinVar: Mar 14, 2021 Last updated: Jul 15, 2024 |
Comment:
CFTR: BP4, BP7
Number of individuals with the variant: 5
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740109.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931256.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001952772.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963662.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely benign
(Mar 21, 2018)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002075908.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
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Likely benign
(Mar 29, 2021)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorder
Affected status: yes
Allele origin:
germline
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Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals
Accession: SCV002029153.1
First in ClinVar: Dec 04, 2021 Last updated: Dec 04, 2021 |
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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 novel complex allele [A238V;F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies. | Diana A | Journal of human genetics | 2016 | PMID: 26911355 |
Validation of a semiconductor next-generation sequencing assay for the clinical genetic screening of CFTR. | Trujillano D | Molecular genetics & genomic medicine | 2015 | PMID: 26436105 |
Next generation diagnostics of cystic fibrosis and CFTR-related disorders by targeted multiplex high-coverage resequencing of CFTR. | Trujillano D | Journal of medical genetics | 2013 | PMID: 23687349 |
Symmetric snapback primers for scanning and genotyping of the cystic fibrosis transmembrane conductance regulator gene. | Zhou L | Clinical chemistry | 2013 | PMID: 23503723 |
The cystic fibrosis gene: a molecular genetic perspective. | Tsui LC | Cold Spring Harbor perspectives in medicine | 2013 | PMID: 23378595 |
Validation of high-resolution DNA melting analysis for mutation scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. | Audrezet MP | The Journal of molecular diagnostics : JMD | 2008 | PMID: 18687795 |
Scanning the cystic fibrosis transmembrane conductance regulator gene using high-resolution DNA melting analysis. | Montgomery J | Clinical chemistry | 2007 | PMID: 17890437 |
Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men. | Dinić J | Vojnosanitetski pregled | 2007 | PMID: 17580535 |
Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations. | Pompei F | European journal of human genetics : EJHG | 2006 | PMID: 16251901 |
Complete gene scanning by temperature gradient capillary electrophoresis using the cystic fibrosis transmembrane conductance regulator gene as a model. | Chou LS | The Journal of molecular diagnostics : JMD | 2005 | PMID: 15681482 |
A large-scale study of the random variability of a coding sequence: a study on the CFTR gene. | Modiano G | European journal of human genetics : EJHG | 2005 | PMID: 15536480 |
Involvement of CFTR gene alterations in obstructive and nonobstructive infertility in men. | Ravnik-Glavac M | Genetic testing | 2001 | PMID: 11788091 |
Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens. | Casals T | Human reproduction (Oxford, England) | 2000 | PMID: 10875853 |
A new approach for identifying non-pathogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals. | Bombieri C | Human genetics | 2000 | PMID: 10746558 |
Complete mutational screening of the CFTR gene in 120 patients with pulmonary disease. | Bombieri C | Human genetics | 1998 | PMID: 9921909 |
Analysis of the complete coding region of the CFTR gene in a cohort of CF patients from north-eastern Italy: identification of 90% of the mutations. | Bonizzato A | Human genetics | 1995 | PMID: 7535742 |
Molecular characterization of cystic fibrosis: 16 novel mutations identified by analysis of the whole cystic fibrosis conductance transmembrane regulator (CFTR) coding regions and splice site junctions. | Fanen P | Genomics | 1992 | PMID: 1379210 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR | - | - | - | - |
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Text-mined citations for rs1800131 ...
HelpRecord last updated Jul 29, 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.