rs8121

Positions:

• chr17-16422654-A-G
• chr17-16422654-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.390A>G​(p.Gly130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,554 control chromosomes in the GnomAD database, including 128,166 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 0.45 (16074 hom., cov: 33)
  • Exomes 𝑓: 0.39 (112092 hom.)
• Consequence: TRPV2 NM_016113.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781

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=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.781 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV2	NM_016113.5	c.390A>G	p.Gly130=	synonymous_variant	4/15	ENST00000338560.12	NP_057197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV2	ENST00000338560.12	c.390A>G	p.Gly130=	synonymous_variant	4/15	1	NM_016113.5	ENSP00000342222	P1
TRPV2	ENST00000455666.1	c.264A>G	p.Gly88=	synonymous_variant	3/4	3		ENSP00000390014

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67856 AN: 151976 Hom.: 16047 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.399

GnomAD3 exomes AF: 0.372 AC: 93023 AN: 250212 Hom.: 18408 AF XY: 0.364 AC XY: 49262 AN XY: 135242

Gnomad AFR exome AF: 0.603

Gnomad AMR exome AF: 0.320

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.230

Gnomad SAS exome AF: 0.250

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.386 AC: 564414 AN: 1461460 Hom.: 112092 Cov.: 53 AF XY: 0.382 AC XY: 277725 AN XY: 726986

Gnomad4 AFR exome AF: 0.608

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.447 AC: 67941 AN: 152094 Hom.: 16074 Cov.: 33 AF XY: 0.443 AC XY: 32964 AN XY: 74354

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.401

Alfa AF: 0.402 Hom.: 20424

Bravo AF: 0.444

Asia WGS AF: 0.260 AC: 905 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs8121; hg19: chr17-16325968; COSMIC: COSV58427735; COSMIC: COSV58427735;