ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3080T>C (p.Ile1027Thr)
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(6); Likely benign(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.3080T>C (p.Ile1027Thr)
Variation ID: 35860 Accession: VCV000035860.68
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117610610 (GRCh38) [ NCBI UCSC ] 7: 117250664 (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 Apr 4, 2013 Aug 4, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3080T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Ile1027Thr missense NC_000007.14:g.117610610T>C NC_000007.13:g.117250664T>C NG_016465.4:g.149827T>C NG_056128.2:g.3664T>C LRG_663:g.149827T>C LRG_663t1:c.3080T>C LRG_663p1:p.Ile1027Thr - Protein change
- Other names
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- Canonical SPDI
- NC_000007.14:117610609:T:C
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00315
Exome Aggregation Consortium (ExAC) 0.00019
The Genome Aggregation Database (gnomAD), exomes 0.00025
Trans-Omics for Precision Medicine (TOPMed) 0.00033
The Genome Aggregation Database (gnomAD) 0.00038
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 |
3806 | 5170 | |
LOC111674472 | - | - | - | GRCh38 | - | 398 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000029515.23 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Dec 18, 2012 | RCV000078993.25 | |
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
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Sep 26, 2023 | RCV000224628.46 | |
CFTR-related disorder
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Likely benign (2) |
criteria provided, single submitter
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Aug 17, 2017 | RCV001163494.14 |
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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Benign
(Dec 18, 2012)
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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: SCV000110862.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 9
Sex: mixed
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Likely benign
(May 16, 2022)
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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: SCV000889306.5
First in ClinVar: Jun 08, 2016 Last updated: Jan 06, 2024 |
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Benign
(Jan 27, 2015)
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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: SCV001179778.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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, 2022)
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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: SCV001155240.25
First in ClinVar: Feb 03, 2020 Last updated: Aug 04, 2024 |
Comment:
CFTR: BS2
Number of individuals with the variant: 4
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Likely Benign
(Dec 28, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281423.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Comment:
Converted during submission to Likely benign.
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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: SCV000304487.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Sep 15, 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: SCV001167225.1
First in ClinVar: Mar 09, 2020 Last updated: Mar 09, 2020 |
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Likely benign
(May 20, 2020)
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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: SCV001810778.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23523379, 30527892, 31808782, … (more)
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23523379, 30527892, 31808782, 22137130, 11354633, 19774621, 11729110, 31350925, 27022295, 17035430, 26574590, 8956039, 26911355, 15858154, 16283887, 17825628, 23951356, 23974870, 21520337) (less)
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Uncertain significance
(Aug 01, 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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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004099270.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
BP2
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Benign
(May 28, 2019)
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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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Mendelics
Accession: SCV001137491.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely benign
(Aug 17, 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: SCV001325541.1
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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely 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: SCV000285002.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
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Benign
(Sep 26, 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: SCV000603024.8
First in ClinVar: Jun 08, 2016 Last updated: Feb 20, 2024 |
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Benign
(Mar 18, 2014)
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no assertion criteria provided
Method: clinical testing
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Cystic Fibrosis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052166.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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Likely benign
(Mar 31, 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: SCV002083590.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Caution advised in the use of CFTR modulator treatment for individuals harboring specific CFTR variants. | Raraigh KS | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2022 | PMID: 35527187 |
High frequency of complex CFTR alleles associated with c.1521_1523delCTT (F508del) in Russian cystic fibrosis patients. | Petrova NV | BMC genomics | 2022 | PMID: 35365085 |
Quantitative Evaluation of CFTR Pre-mRNA Splicing Dependent on the (TG)mTn Poly-Variant Tract. | Sterrantino M | Diagnostics (Basel, Switzerland) | 2021 | PMID: 33504063 |
Treatment of Cystic Fibrosis Patients Homozygous for F508del with Lumacaftor-Ivacaftor (Orkambi(®)) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells. | Favia M | International journal of molecular sciences | 2020 | PMID: 32244302 |
The influence of CFTR complex alleles on precision therapy of cystic fibrosis. | Chevalier B | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2020 | PMID: 31883651 |
CFTR: New insights into structure and function and implications for modulation by small molecules. | Kleizen B | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2020 | PMID: 31759907 |
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 |
Pitfalls in the interpretation of CFTR variants in the context of incidental findings. | Boussaroque A | Human mutation | 2019 | PMID: 31350925 |
Predictive factors for lumacaftor/ivacaftor clinical response. | Masson A | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2019 | PMID: 30595473 |
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 |
Newborn Screening for Cystic Fibrosis in California. | Kharrazi M | Pediatrics | 2015 | PMID: 26574590 |
Full-open and closed CFTR channels, with lateral tunnels from the cytoplasm and an alternative position of the F508 region, as revealed by molecular dynamics. | Mornon JP | Cellular and molecular life sciences : CMLS | 2015 | PMID: 25287046 |
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients. | Masson E | PloS one | 2013 | PMID: 23951356 |
Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. | Steiner B | Human mutation | 2011 | PMID: 21520337 |
Estimating the age of CFTR mutations predominantly found in Brittany (Western France). | Fichou Y | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 17825628 |
CFTR gene analysis in Latin American CF patients: heterogeneous origin and distribution of mutations across the continent. | Pérez MM | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2007 | PMID: 16963320 |
Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection. | Ziedalski TM | Chest | 2006 | PMID: 17035430 |
Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. | Schrijver I | The Journal of molecular diagnostics : JMD | 2005 | PMID: 15858154 |
CFTR gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease. | Tzetis M | Human genetics | 2001 | PMID: 11354633 |
Mutation characterization of CFTR gene in 206 Northern Irish CF families: thirty mutations, including two novel, account for approximately 94% of CF chromosomes. | Hughes DJ | Human mutation | 1996 | PMID: 8956039 |
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 rs1800112 ...
HelpRecord last updated Sep 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.