7-117542102-G-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000492.4(CFTR):c.1203G>A(p.Trp401Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,419,634 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 (★★★). 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.1203G>A | p.Trp401Ter | stop_gained | 9/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.1203G>A | p.Trp401Ter | stop_gained | 9/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250608Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135534
GnomAD4 exome AF: 0.00000211 AC: 3AN: 1419634Hom.: 0 Cov.: 24 AF XY: 0.00000141 AC XY: 1AN XY: 708962
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cystic fibrosis Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2015 | The p.W401* pathogenic mutation (also known as c.1203G>A), located in coding exon 9 of the CFTR gene, results from a G to A substitution at nucleotide position 1203. This changes the amino acid from a tryptophan to a stop codon within coding exon 9. This pathogenic mutation is associated with elevated sweat chloride levels, pancreatic insufficiency (PI), and decreased lung function (Sosnay PR et al. Nat Genet. 2013;45(10):1160-7, Supplementary Table and The Clinical and Functional Translation of CFTR (CFTR2); available at http://cftr2.org. Accessed April 2, 2015). In addition to the clinical data available in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). - |
Pathogenic, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | - - |
Pathogenic, reviewed by expert panel | research | CFTR2 | Mar 17, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 18, 2022 | This sequence change creates a premature translational stop signal (p.Trp401*) 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 (rs397508175, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 7508414, 23974870). ClinVar contains an entry for this variant (Variation ID: 53213). For these reasons, this variant has been classified as Pathogenic. - |
CFTR-related disorder Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 17, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at