12-109796853-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021625.5(TRPV4):c.1153-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 811,798 control chromosomes in the GnomAD database, including 39,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 6202 hom., cov: 32)

Exomes 𝑓: 0.30 ( 33216 hom. )

Consequence

TRPV4
NM_021625.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.48

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

metatropic dysplasia
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen
neuromuscular disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
spondylometaphyseal dysplasia, Kozlowski type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet
TRPV4-related bone disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
autosomal dominant brachyolmia
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
Charcot-Marie-Tooth disease axonal type 2C
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
brachyolmia
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
scapuloperoneal spinal muscular atrophy, autosomal dominant
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
spondyloepimetaphyseal dysplasia, Maroteaux type
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
familial avascular necrosis of femoral head
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial digital arthropathy-brachydactyly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
neuronopathy, distal hereditary motor, autosomal dominant 8
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
parastremmatic dwarfism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRPV4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 12-109796853-T-C is Benign according to our data. Variant chr12-109796853-T-C is described in ClinVar as Benign. ClinVar VariationId is 670253.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021625.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPV4	NM_021625.5	MANE Select	c.1153-149A>G	intron	N/A	NP_067638.3
TRPV4	NM_001177431.1		c.1051-149A>G	intron	N/A	NP_001170902.1	Q9HBA0-5
TRPV4	NM_001177428.1		c.1012-149A>G	intron	N/A	NP_001170899.1	Q9HBA0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPV4	ENST00000261740.7	TSL:1 MANE Select	c.1153-149A>G	intron	N/A	ENSP00000261740.2	Q9HBA0-1
TRPV4	ENST00000418703.7	TSL:1	c.1153-149A>G	intron	N/A	ENSP00000406191.2	Q9HBA0-1
TRPV4	ENST00000536838.1	TSL:1	c.1051-149A>G	intron	N/A	ENSP00000444336.1	Q9HBA0-5

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39773

AN:

151976

Hom.:

6196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.264

GnomAD4 exome

AF:

0.297

AC:

196217

AN:

659704

Hom.:

33216

AF XY:

0.297

AC XY:

98780

AN XY:

332414

show subpopulations

African (AFR)

AF:

0.118

AC:

1966

AN:

16650

American (AMR)

AF:

0.243

AC:

4281

AN:

17646

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

4353

AN:

14536

East Asian (EAS)

AF:

0.687

AC:

21482

AN:

31266

South Asian (SAS)

AF:

0.254

AC:

10408

AN:

40960

European-Finnish (FIN)

AF:

0.347

AC:

9742

AN:

28046

Middle Eastern (MID)

AF:

0.305

AC:

746

AN:

2442

European-Non Finnish (NFE)

AF:

0.281

AC:

133611

AN:

475570

Other (OTH)

AF:

0.295

AC:

9628

AN:

32588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6269

12537

18806

25074

31343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3198

6396

9594

12792

15990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.262

AC:

39783

AN:

152094

Hom.:

6202

Cov.:

AF XY:

0.269

AC XY:

20011

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.126

AC:

5233

AN:

41530

American (AMR)

AF:

0.279

AC:

4257

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1082

AN:

3470

East Asian (EAS)

AF:

0.688

AC:

3540

AN:

5144

South Asian (SAS)

AF:

0.273

AC:

1314

AN:

4816

European-Finnish (FIN)

AF:

0.348

AC:

3678

AN:

10580

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19648

AN:

67968

Other (OTH)

AF:

0.265

AC:

560

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1437

2874

4312

5749

7186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.276

Hom.:

16785

Bravo

AF:

0.252

Asia WGS

AF:

0.376

AC:

1307

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.2

(source)

DANN

Benign

0.39

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over