rs121908805
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000492.4(CFTR):c.1397C>A(p.Ser466Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S466S) has been classified as Likely 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.1397C>A | p.Ser466Ter | stop_gained | 11/27 | ENST00000003084.11 | |
CFTR-AS1 | NR_149084.1 | n.221+1265G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.1397C>A | p.Ser466Ter | stop_gained | 11/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1446926Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 720972
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cystic fibrosis Pathogenic:1
Pathogenic, reviewed by expert panel | research | CFTR2 | Mar 17, 2017 | - - |
Cystic fibrosis;na:CFTR-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both - |
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