rs397508602
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000492.4(CFTR):c.3745G>A(p.Gly1249Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★).
Frequency
Consequence
NM_000492.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.3745G>A | p.Gly1249Arg | missense_variant | 23/27 | ENST00000003084.11 | NP_000483.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.3745G>A | p.Gly1249Arg | missense_variant | 23/27 | 1 | NM_000492.4 | ENSP00000003084.6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251006Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135646
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461366Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726980
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cystic fibrosis Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | - - |
not provided, no classification provided | literature only | ClinVar Staff, National Center for Biotechnology Information (NCBI) | - | - - |
Pathogenic, reviewed by expert panel | research | CFTR2 | Mar 11, 2019 | - - |
CFTR-related disorder Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at