Genetic Variant NM_016113.5:c.427A>C (chr17-16422691-A-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_016113.5(TRPV2):c.427A>C(p.Arg143Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,610,794 control chromosomes in the GnomAD database, including 125,044 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14879 hom., cov: 33)

Exomes 𝑓: 0.38 ( 110165 hom. )

Consequence

TRPV2
NM_016113.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.783

Publications

18 publications found

Variant links:

Genes affected

TRPV2 (HGNC:18082): (transient receptor potential cation channel subfamily V member 2) This gene encodes an ion channel that is activated by high temperatures above 52 degrees Celsius. The protein may be involved in transduction of high-temperature heat responses in sensory ganglia. It is thought that in other tissues the channel may be activated by stimuli other than heat. [provided by RefSeq, Jul 2008]

TRPV2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.078).

BP7

Synonymous conserved (PhyloP=-0.783 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV2	NM_016113.5 link	c.427A>C	p.Arg143Arg	synonymous_variant	Exon 4 of 15	ENST00000338560.12	NP_057197.2	Q9Y5S1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV2	ENST00000338560.12 link	c.427A>C	p.Arg143Arg	synonymous_variant	Exon 4 of 15	1	NM_016113.5	ENSP00000342222.7		Q9Y5S1
TRPV2	ENST00000455666.1 link	c.298A>C	p.Arg100Arg	synonymous_variant	Exon 3 of 4	3		ENSP00000390014.1		H7BZK2

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65704

AN:

151990

Hom.:

14860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.387

GnomAD2 exomes

AF:

0.365

AC:

89580

AN:

245518

AF XY:

0.358

show subpopulations

Gnomad AFR exome

AF:

0.550

Gnomad AMR exome

AF:

0.311

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.386

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.384

AC:

559546

AN:

1458686

Hom.:

110165

Cov.:

AF XY:

0.379

AC XY:

275241

AN XY:

725316

show subpopulations

African (AFR)

AF:

0.558

AC:

18626

AN:

33398

American (AMR)

AF:

0.317

AC:

14026

AN:

44288

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

10788

AN:

26078

East Asian (EAS)

AF:

0.219

AC:

8663

AN:

39604

South Asian (SAS)

AF:

0.246

AC:

21082

AN:

85778

European-Finnish (FIN)

AF:

0.469

AC:

24933

AN:

53216

Middle Eastern (MID)

AF:

0.355

AC:

2045

AN:

5764

European-Non Finnish (NFE)

AF:

0.393

AC:

436398

AN:

1110282

Other (OTH)

AF:

0.381

AC:

22985

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21129

42259

63388

84518

105647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13528

27056

40584

54112

67640

<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:

0.432

AC:

65779

AN:

152108

Hom.:

14879

Cov.:

AF XY:

0.429

AC XY:

31933

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.553

AC:

22961

AN:

41496

American (AMR)

AF:

0.363

AC:

5548

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1522

AN:

3472

East Asian (EAS)

AF:

0.237

AC:

1225

AN:

5174

South Asian (SAS)

AF:

0.243

AC:

1171

AN:

4826

European-Finnish (FIN)

AF:

0.473

AC:

4997

AN:

10570

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27156

AN:

67980

Other (OTH)

AF:

0.389

AC:

821

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1907

3813

5720

7626

9533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.414

Hom.:

10888

Bravo

AF:

0.428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.1

(source)

DANN

Benign

0.68

PhyloP100

-0.78

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over