ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3209G>C (p.Arg1070Pro)
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.3209G>C (p.Arg1070Pro)
Variation ID: 53686 Accession: VCV000053686.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117611650 (GRCh38) [ NCBI UCSC ] 7: 117251704 (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 Jan 25, 2018 Feb 14, 2024 Jun 6, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3209G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Arg1070Pro missense NC_000007.14:g.117611650G>C NC_000007.13:g.117251704G>C NG_016465.4:g.150867G>C NG_056128.2:g.4704G>C LRG_663:g.150867G>C LRG_663t1:c.3209G>C LRG_663p1:p.Arg1070Pro P13569:p.Arg1070Pro - Protein change
- R1070P
- Other names
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- Canonical SPDI
- NC_000007.14:117611649:G: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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0.00120 (A)
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Allele frequency
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The frequency of the allele represented by this VCV record.
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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 |
3825 | 5200 | |
LOC111674472 | - | - | - | GRCh38 | - | 400 |
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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Likely pathogenic (2) |
criteria provided, single submitter
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Jun 6, 2022 | RCV000577217.4 |
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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Likely pathogenic
(Jun 06, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003440721.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This variant disrupts the p.Arg1070 amino acid residue in CFTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7539342, 9239681, … (more)
This variant disrupts the p.Arg1070 amino acid residue in CFTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7539342, 9239681, 9598638, 10875853, 15070876, 16189704, 18951463, 20460946, 20880762, 21520337, 23891399, 23974870, 27171515). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects CFTR function (PMID: 10762539, 18951463). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 53686). This variant is also known as c.3341G>C. This missense change has been observed in individuals with cystic fibrosis (PMID: 9401006, 18951463). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1070 of the CFTR protein (p.Arg1070Pro). (less)
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not provided
(-)
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no classification provided
Method: literature only
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CFTR-related disorders
Affected status: yes
Allele origin:
germline
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ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000679056.1
First in ClinVar: Jan 25, 2018 Last updated: Jan 25, 2018 |
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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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Genophenotypic Analysis of Pediatric Patients With Acute Recurrent and Chronic Pancreatitis. | Palermo JJ | Pancreas | 2016 | PMID: 27171515 |
Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. | Van Goor F | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2014 | PMID: 23891399 |
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. | Steiner B | Human mutation | 2011 | PMID: 21520337 |
[R74W;R1070W;D1270N]: a new complex allele responsible for cystic fibrosis. | de Prada Merino A | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2010 | PMID: 20880762 |
CFTR gene mutation in patients with apparently idiopathic pancreatitis: lack of phenotype-genotype correlation. | Pelletier AL | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] | 2010 | PMID: 20460946 |
Localization studies of rare missense mutations in cystic fibrosis transmembrane conductance regulator (CFTR) facilitate interpretation of genotype-phenotype relationships. | Krasnov KV | Human mutation | 2008 | PMID: 18951463 |
Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples. | McGinniss MJ | Human genetics | 2005 | PMID: 16189704 |
Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens. | Dayangaç D | Human reproduction (Oxford, England) | 2004 | PMID: 15070876 |
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 |
Effects of cystic fibrosis and congenital bilateral absence of the vas deferens-associated mutations on cystic fibrosis transmembrane conductance regulator-mediated regulation of separate channels. | Mickle JE | American journal of human genetics | 2000 | PMID: 10762539 |
Correlation between genito-urinary anomalies, semen analysis and CFTR genotype in patients with congenital bilateral absence of the vas deferens. | de la Taille A | British journal of urology | 1998 | PMID: 9598638 |
Cystic fibrosis mutation frequencies in upstate New York. | Shrimpton AE | Human mutation | 1997 | PMID: 9401006 |
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 |
Structural analysis of CFTR gene in congenital bilateral absence of vas deferens. | Jézéquel P | Clinical chemistry | 1995 | PMID: 7539342 |
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Text-mined citations for rs78769542 ...
HelpRecord last updated Sep 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.