rs773790621
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000492.4(CFTR):āc.766A>Gā(p.Ser256Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,599,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. S256S) has been classified as Likely benign.
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.766A>G | p.Ser256Gly | missense_variant | 7/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.766A>G | p.Ser256Gly | missense_variant | 7/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000520 AC: 12AN: 230864Hom.: 0 AF XY: 0.0000803 AC XY: 10AN XY: 124456
GnomAD4 exome AF: 0.0000276 AC: 40AN: 1446850Hom.: 0 Cov.: 31 AF XY: 0.0000376 AC XY: 27AN XY: 718730
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Cystic fibrosis Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 14, 2022 | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 256 of the CFTR protein (p.Ser256Gly). This variant is present in population databases (rs773790621, gnomAD 0.04%). 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: 582520). 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 | May 04, 2023 | The p.S256G variant (also known as c.766A>G), located in coding exon 7 of the CFTR gene, results from an A to G substitution at nucleotide position 766. The serine at codon 256 is replaced by glycine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
CFTR-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 08, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at