rs145460865
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_021625.5(TRPV4):c.1891+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,528,462 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0047 ( 3 hom., cov: 31)
Exomes 𝑓: 0.0058 ( 51 hom. )
Consequence
TRPV4
NM_021625.5 intron
NM_021625.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0680
Genes affected
TRPV4 (HGNC:18083): (transient receptor potential cation channel subfamily V member 4) This gene encodes a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels. The encoded protein is a Ca2+-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure. Mutations in this gene are the cause of spondylometaphyseal and metatropic dysplasia and hereditary motor and sensory neuropathy type IIC. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 12-109792316-G-A is Benign according to our data. Variant chr12-109792316-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00468 (703/150198) while in subpopulation NFE AF= 0.00706 (478/67742). AF 95% confidence interval is 0.00653. There are 3 homozygotes in gnomad4. There are 341 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 703 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRPV4 | NM_021625.5 | c.1891+47C>T | intron_variant | ENST00000261740.7 | NP_067638.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRPV4 | ENST00000261740.7 | c.1891+47C>T | intron_variant | 1 | NM_021625.5 | ENSP00000261740 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00468 AC: 703AN: 150146Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.00585 AC: 1451AN: 248022Hom.: 12 AF XY: 0.00589 AC XY: 792AN XY: 134486
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GnomAD4 exome AF: 0.00576 AC: 7944AN: 1378264Hom.: 51 Cov.: 26 AF XY: 0.00569 AC XY: 3921AN XY: 689254
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GnomAD4 genome AF: 0.00468 AC: 703AN: 150198Hom.: 3 Cov.: 31 AF XY: 0.00466 AC XY: 341AN XY: 73188
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 27, 2018 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at