ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.1029del (p.Phe342_Cys343insTer)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.1029del (p.Phe342_Cys343insTer)
Variation ID: 53170 Accession: VCV000053170.25
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117540259 (GRCh38) [ NCBI UCSC ] 7: 117180313 (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 Mar 29, 2015 Jun 17, 2024 Mar 17, 2017 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.1029del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Phe342_Cys343insTer nonsense NM_000492.4:c.1029delC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000492.3:c.1029delC NC_000007.14:g.117540259del NC_000007.13:g.117180313del NG_016465.4:g.79476del LRG_663:g.79476del LRG_663t1:c.1029del - Protein change
- Other names
- 1161delC
- Canonical SPDI
- NC_000007.14:117540258: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.
1000 Genomes Project 30x 0.00016
The Genome Aggregation Database (gnomAD) 0.00000
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00006
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
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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 |
3712 | 5035 |
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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Pathogenic (7) |
reviewed by expert panel
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Mar 17, 2017 | RCV000046204.18 | |
CFTR-related disorder
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Pathogenic (1) |
no assertion criteria provided
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May 20, 2019 | RCV001027900.1 |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 7, 2022 | RCV001508220.8 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV003221797.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 14, 2023 | RCV003473442.2 |
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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Pathogenic
(Mar 17, 2017)
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reviewed by expert panel
Method: research
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR2
Study: CFTR2
Accession: SCV000245932.2 First in ClinVar: Sep 23, 2015 Last updated: Dec 12, 2017 |
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Pathogenic
(Jan 29, 2018)
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criteria provided, single submitter
Method: curation
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cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR-France
Accession: SCV001169457.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
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Pathogenic
(Jul 10, 2014)
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criteria provided, single submitter
Method: literature only
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Cystic fibrosis
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220498.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pancreatitis
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Lifecell International Pvt. Ltd
Accession: SCV003915946.1
First in ClinVar: Apr 23, 2023 Last updated: Apr 23, 2023 |
Comment:
A Heterozygous Frameshift variant c.1029delC in Exon 8 of the CFTR gene that results in the premature termination of the protein (p.Cys343fs*1) was identified. The … (more)
A Heterozygous Frameshift variant c.1029delC in Exon 8 of the CFTR gene that results in the premature termination of the protein (p.Cys343fs*1) was identified. The observed variant has a minor allele frequency of 0.00006% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. The variant was found in ClinVar (Variant ID :53170) with a classification of Pathogenic and a review status of (3 star) criteria provided, expert panel reviewed. The variant was previously reported by Malone G et al.,1998. Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. (less)
Ethnicity/Population group: Asian
Geographic origin: India
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Pathogenic
(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: SCV001584168.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Cys343*) in the CFTR gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Cys343*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is present in population databases (rs121908774, gnomAD 0.05%). This premature translational stop signal has been observed in individuals with cystic fibrosis (PMID: 9482579, 15463906). This variant is also known as c.1161delC. ClinVar contains an entry for this variant (Variation ID: 53170). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Dec 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bronchiectasis with or without elevated sweat chloride 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004213388.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Mar 11, 2021)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001714229.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PVS1, PM2, PP5, PM3_Strong
Number of individuals with the variant: 1
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Pathogenic
(Jun 14, 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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004020671.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
Variant summary: CFTR c.1029delC (p.Cys343X) results in a premature termination codon, predicted to cause an absence of the protein due to nonsense mediated decay, which … (more)
Variant summary: CFTR c.1029delC (p.Cys343X) results in a premature termination codon, predicted to cause an absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 6.4e-05 in 251216 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CFTR causing Cystic Fibrosis (6.4e-05 vs 0.013), allowing no conclusion about variant significance. c.1029delC has been reported in the literature in multiple individuals affected with Cystic Fibrosis (example, Malone_1998, Ooi_2012, Indika_2019). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 31126253, 9482579, 22658665). Multiple clinical diagnostic laboratories and databases (CFTR2, CFTR-France) have submitted clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Mar 07, 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: SCV002019224.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 15, 2016)
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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: SCV002693299.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1029delC pathogenic mutation, located in coding exon 8 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 1029, causing … (more)
The c.1029delC pathogenic mutation, located in coding exon 8 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 1029, causing a translational frameshift with a predicted alternate stop codon (p.C343*). This mutation was identified in the homozygous state in two unrelated sibling pairs with cystic fibrosis (Malone G et al. Hum. Mutat., 1998;11:152-7). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005042712.1
First in ClinVar: May 12, 2024 Last updated: May 12, 2024 |
Comment:
The frameshift c.1029del p.Cys343Ter variant in the CFTR gene has been observed in individuals with cystic fibrosis Duguépéroux, Ingrid et al., 2004. This variant is … (more)
The frameshift c.1029del p.Cys343Ter variant in the CFTR gene has been observed in individuals with cystic fibrosis Duguépéroux, Ingrid et al., 2004. This variant is reported with the allele frequency 0.006% in the gnomAD Exomes and novel in 1000 Genomes. It is submitted to ClinVar as Pathogenic multiple submissions. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Abnormality of the liver (present)
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Pathogenic
(May 20, 2019)
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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: SCV001190623.1
First in ClinVar: Mar 29, 2020 Last updated: Mar 29, 2020 |
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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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Phenotypic spectrum and genetic heterogeneity of cystic fibrosis in Sri Lanka. | Indika NLR | BMC medical genetics | 2019 | PMID: 31126253 |
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. | Lazarin GA | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22975760 |
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. | Ooi CY | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2012 | PMID: 22658665 |
Variation in MSRA modifies risk of neonatal intestinal obstruction in cystic fibrosis. | Henderson LB | PLoS genetics | 2012 | PMID: 22438829 |
Identification and characterization of CFTR gene mutations in Indian CF patients. | Sharma N | Annals of human genetics | 2009 | PMID: 18782298 |
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. | Castellani C | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 18456578 |
Characterisation of mutations and genotype-phenotype correlation in cystic fibrosis: experience from India. | Shastri SS | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 17716958 |
Cystic fibrosis at the Reunion Island (France): spectrum of mutations and genotype-phenotype for the Y122X mutation. | Duguépéroux I | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2004 | PMID: 15463906 |
Cystic fibrosis transmembrane regulator gene mutations in Bahrain. | Eskandarani HA | Journal of tropical pediatrics | 2002 | PMID: 12521276 |
Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening. | Bobadilla JL | Human mutation | 2002 | PMID: 12007216 |
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. | Cohn JA | The New England journal of medicine | 1998 | PMID: 9725922 |
Detection of five novel mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in Pakistani patients with cystic fibrosis: Y569D, Q98X, 296+12(T>C), 1161delC and 621+2(T>C). | Malone G | Human mutation | 1998 | PMID: 9482579 |
Genotype-phenotype relationships in a cohort of adult cystic fibrosis patients. | Hubert D | The European respiratory journal | 1996 | PMID: 8947061 |
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR. | Yang Y | Human molecular genetics | 1993 | PMID: 7691345 |
A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. | Cutting GR | Nature | 1990 | PMID: 1695717 |
https://cftr2.org | - | - | - | - |
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Text-mined citations for rs121908774 ...
HelpRecord last updated Jun 17, 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.