7-117592541-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000492.4(CFTR):c.2374C>T(p.Arg792Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000329 in 1,520,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★). Synonymous variant affecting the same amino acid position (i.e. R792R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000492.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.2374C>T | p.Arg792Ter | stop_gained | 14/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.2374C>T | p.Arg792Ter | stop_gained | 14/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000552 AC: 1AN: 181308Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 95510
GnomAD4 exome AF: 0.00000292 AC: 4AN: 1368778Hom.: 0 Cov.: 32 AF XY: 0.00000298 AC XY: 2AN XY: 671288
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74308
ClinVar
Submissions by phenotype
Cystic fibrosis Pathogenic:7
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | Nov 05, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jul 25, 2017 | - - |
Pathogenic, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Johns Hopkins Genomics, Johns Hopkins University | Jan 27, 2020 | Disease-causing CFTR variant. See www.CFTR2.org for phenotype information. - |
Pathogenic, reviewed by expert panel | research | CFTR2 | Mar 17, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 10, 2023 | The p.R792* pathogenic mutation (also known as c.2374C>T), located in coding exon 14 of the CFTR gene, results from a C to T substitution at nucleotide position 2374. This changes the amino acid from an arginine to a stop codon within coding exon 14. This mutation was first detected in an individual with cystic fibrosis; however, the presence of a second CFTR variant was not reported (Claustres M et al. Hum Mol Genet, 1993 Aug;2:1209-13). This variant has been reported in multiple individuals with an elevated sweat chloride level in The Clinical and Functional TRanslation of CFTR (CFTR2) database (available at http://cftr2.org. Accessed 3/9/2023). 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. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 25, 2023 | This sequence change creates a premature translational stop signal (p.Arg792*) 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 (rs145449046, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with cystic fibrosis (PMID: 7691344, 27081564, 28603918). ClinVar contains an entry for this variant (Variation ID: 53483). For these reasons, this variant has been classified as Pathogenic. - |
not specified Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 08, 2018 | Variant summary: CFTR c.2374C>T (p.Arg792X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.2491G>T, p.Glu831X; c.2551C>T, p.Arg851X; c.2554dupT, p.Tyr852fsX44). The variant was absent in 110418 control chromosomes (ExAC). The variant has been reported in CF patients in the literature in trans with pathogenic CFTR variants (Claustres_2000, des Georges_2004, Sanchez_2016, Shen_2016, Tian_2016, and Filleron_2011). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, which classified it as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Cystic fibrosis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | - | - - |
CFTR-related disorder Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 17, 2017 | - - |
Bronchiectasis with or without elevated sweat chloride 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at