rs1129235

Positions:

• chr17-16422691-A-C
• chr17-16422691-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016113.5(TRPV2):​c.427A>C​(p.Arg143=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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/exons	MANE	UniProt
TRPV2	NM_016113.5	c.427A>C	p.Arg143=	synonymous_variant	4/15	ENST00000338560.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV2	ENST00000338560.12	c.427A>C	p.Arg143=	synonymous_variant	4/15	1	NM_016113.5	P1
TRPV2	ENST00000455666.1	c.301A>C	p.Arg101=	synonymous_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65704 AN: 151990 Hom.: 14860 Cov.: 33

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

GnomAD3 exomes AF: 0.365 AC: 89580 AN: 245518 Hom.: 17125 AF XY: 0.358 AC XY: 47535 AN XY: 132634

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 SAS exome AF: 0.241

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.: 55 AF XY: 0.379 AC XY: 275241 AN XY: 725316

Gnomad4 AFR exome AF: 0.558

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.432 AC: 65779 AN: 152108 Hom.: 14879 Cov.: 33 AF XY: 0.429 AC XY: 31933 AN XY: 74354

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.389

Alfa AF: 0.412 Hom.: 7969

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
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs1129235; hg19: chr17-16326005; COSMIC: COSV58428410; COSMIC: COSV58428410;