Variant 12-109783826-G-C 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.2459-48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,601,946 control chromosomes in the GnomAD database, including 209,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19167 hom., cov: 28)

Exomes 𝑓: 0.51 ( 190275 hom. )

Consequence

TRPV4
NM_021625.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.34

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=-0.89).

BP6

Variant 12-109783826-G-C is Benign according to our data. Variant chr12-109783826-G-C is described in ClinVar as [Benign]. Clinvar id is 261417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-109783826-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV4	NM_021625.5 link	c.2459-48C>G		intron_variant		ENST00000261740.7	NP_067638.3	Q9HBA0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV4	ENST00000261740.7 link	c.2459-48C>G		intron_variant		1	NM_021625.5	ENSP00000261740.2		Q9HBA0-1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75641

AN:

151374

Hom.:

19144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.522

GnomAD3 exomes

AF:

0.536

AC:

129580

AN:

241558

Hom.:

35536

AF XY:

0.543

AC XY:

71206

AN XY:

131238

show subpopulations

Gnomad AFR exome

AF:

0.444

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.748

Gnomad SAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.534

GnomAD4 exome

AF:

0.509

AC:

738072

AN:

1450454

Hom.:

190275

Cov.:

AF XY:

0.514

AC XY:

370643

AN XY:

721694

show subpopulations

Gnomad4 AFR exome

AF:

0.443

Gnomad4 AMR exome

AF:

0.497

Gnomad4 ASJ exome

AF:

0.517

Gnomad4 EAS exome

AF:

0.757

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.512

Gnomad4 NFE exome

AF:

0.492

Gnomad4 OTH exome

AF:

0.512

GnomAD4 genome

AF:

0.500

AC:

75705

AN:

151492

Hom.:

19167

Cov.:

AF XY:

0.507

AC XY:

37541

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.523

Gnomad4 EAS

AF:

0.755

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.497

Gnomad4 NFE

AF:

0.495

Gnomad4 OTH

AF:

0.524

Alfa

AF:

0.419

Hom.:

2164

Bravo

AF:

0.497

Asia WGS

AF:

0.643

AC:

2231

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.055

DANN

Benign

0.54

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