Variant rs10850750 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021625.5(TRPV4):c.1584+18G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,434,736 control chromosomes in the GnomAD database, including 50,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3667 hom., cov: 28)

Exomes 𝑓: 0.26 ( 50741 hom. )

Failed GnomAD Quality Control

Consequence

TRPV4
NM_021625.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.705

Variant links:

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]

TRPV4 links:

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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=-0.93).

BP6

Variant 12-109793912-C-G is Benign according to our data. Variant chr12-109793912-C-G is described in ClinVar as [Benign]. Clinvar id is 261414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-109793912-C-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV4	NM_021625.5 linkuse as main transcript	c.1584+18G>C		intron_variant		ENST00000261740.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV4	ENST00000261740.7 linkuse as main transcript	c.1584+18G>C		intron_variant		1	NM_021625.5	P1	Q9HBA0-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

29745

AN:

148466

Hom.:

3664

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.226

AC:

51293

AN:

226850

Hom.:

6299

AF XY:

0.233

AC XY:

28331

AN XY:

121732

show subpopulations

Gnomad AFR exome

AF:

0.0467

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.261

AC:

374489

AN:

1434736

Hom.:

50741

Cov.:

AF XY:

0.262

AC XY:

186592

AN XY:

712480

show subpopulations

Gnomad4 AFR exome

AF:

0.0500

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.274

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.200

AC:

29747

AN:

148584

Hom.:

3667

Cov.:

AF XY:

0.200

AC XY:

14442

AN XY:

72338

show subpopulations

Gnomad4 AFR

AF:

0.0560

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.259

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.0496

Hom.:

166

Bravo

AF:

0.192

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 28, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Charcot-Marie-Tooth disease axonal type 2C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0020

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over