7-117665464-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000492.4(CFTR):āc.4142A>Gā(p.Tyr1381Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000377 in 1,590,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1381H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000492.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.4142A>G | p.Tyr1381Cys | missense_variant | 26/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.4142A>G | p.Tyr1381Cys | missense_variant | 26/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249758Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134948
GnomAD4 exome AF: 0.00000278 AC: 4AN: 1437792Hom.: 0 Cov.: 27 AF XY: 0.00000418 AC XY: 3AN XY: 717048
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
Cystic fibrosis Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 23, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1381 of the CFTR protein (p.Tyr1381Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 411115). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2024 | The p.Y1381C variant (also known as c.4142A>G), located in coding exon 26 of the CFTR gene, results from an A to G substitution at nucleotide position 4142. The tyrosine at codon 1381 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. - |
CFTR-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 20, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at