rs767331924
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_021625.5(TRPV4):c.656G>A(p.Arg219His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R219C) has been classified as Uncertain significance.
Frequency
Consequence
NM_021625.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPV4 | NM_021625.5 | c.656G>A | p.Arg219His | missense_variant | 4/16 | ENST00000261740.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPV4 | ENST00000261740.7 | c.656G>A | p.Arg219His | missense_variant | 4/16 | 1 | NM_021625.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251142Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135804
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461818Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 727198
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74490
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 24, 2017 | This sequence change replaces arginine with histidine at codon 219 of the TRPV4 protein (p.Arg219His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs767331924, ExAC 0.009%) but has not been reported in the literature in individuals with a TRPV4-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at