rs576710089
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000492.4(CFTR):c.3592G>A(p.Val1198Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V1198V) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.3592G>A | p.Val1198Met | missense_variant | 22/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.3592G>A | p.Val1198Met | missense_variant | 22/27 | 1 | NM_000492.4 | P2 | |
ENST00000456270.1 | n.66-11305C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250442Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135310
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461218Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726898
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74438
ClinVar
Submissions by phenotype
Cystic fibrosis Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 30, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1198 of the CFTR protein (p.Val1198Met). This variant is present in population databases (rs576710089, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 29997923). ClinVar contains an entry for this variant (Variation ID: 572626). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 22, 2019 | The CFTR c.3592G>A; p.Val1198Met variant (rs576710089) is reported in the literature in a newborn screening cohort, but no specific clinical symptoms are provided (Prach 2013). This variant is reported in ClinVar (Variation ID: 572626), and is found in the African population with an allele frequency of 0.012% (3/24958 alleles) in the Genome Aggregation Database. The valine at codon 1198 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Val1198Met variant is uncertain at this time. References: Prach L et al. Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California. J Mol Diagn. 2013 Sep;15(5):710-22. - |
CFTR-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 06, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at