rs143502097
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 2P and 18B. PP2PP3BP4_ModerateBP6_Very_StrongBS1BS2
The NM_021625.5(TRPV4):c.1337G>T(p.Arg446Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000149 in 1,613,684 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R446H) has been classified as Uncertain significance.
Frequency
Consequence
NM_021625.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPV4 | NM_021625.5 | c.1337G>T | p.Arg446Leu | missense_variant | 8/16 | ENST00000261740.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPV4 | ENST00000261740.7 | c.1337G>T | p.Arg446Leu | missense_variant | 8/16 | 1 | NM_021625.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000822 AC: 125AN: 152018Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000203 AC: 51AN: 251118Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135752
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461548Hom.: 0 Cov.: 33 AF XY: 0.0000550 AC XY: 40AN XY: 727076
GnomAD4 genome ? AF: 0.000828 AC: 126AN: 152136Hom.: 1 Cov.: 32 AF XY: 0.000780 AC XY: 58AN XY: 74384
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 31, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease axonal type 2C Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 04, 2019 | - - |
TRPV4-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 15, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at