rs8065080

Positions:

• chr17-3577153-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080704.4(TRPV1):​c.1753A>G​(p.Ile585Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,587,278 control chromosomes in the GnomAD database, including 112,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.32 (9134 hom., cov: 33)
  • Exomes 𝑓: 0.37 (103851 hom.)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

Genes affected

TRPV1 (HGNC:12716): (transient receptor potential cation channel subfamily V member 1) Capsaicin, the main pungent ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The protein encoded by this gene is a receptor for capsaicin and is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. This receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo. Four transcript variants encoding the same protein, but with different 5' UTR sequence, have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.778678E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.1753A>G	p.Ile585Val	missense_variant	13/17	ENST00000572705.2
TRPV1	NM_018727.5	c.1753A>G	p.Ile585Val	missense_variant	12/16
TRPV1	NM_080705.4	c.1753A>G	p.Ile585Val	missense_variant	12/16
TRPV1	NM_080706.3	c.1753A>G	p.Ile585Val	missense_variant	11/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.1753A>G	p.Ile585Val	missense_variant	13/17	1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48981 AN: 151856 Hom.: 9137 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.368 AC: 77537 AN: 210474 Hom.: 15368 AF XY: 0.367 AC XY: 41557 AN XY: 113164

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.592

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.438

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.374 AC: 536588 AN: 1435304 Hom.: 103851 Cov.: 38 AF XY: 0.372 AC XY: 264976 AN XY: 711348

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.322 AC: 48985 AN: 151974 Hom.: 9134 Cov.: 33 AF XY: 0.330 AC XY: 24477 AN XY: 74260

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.356

Alfa AF: 0.374 Hom.: 24683

Bravo AF: 0.312

TwinsUK AF: 0.365 AC: 1354

ALSPAC AF: 0.368 AC: 1418

ESP6500AA AF: 0.152 AC: 616

ESP6500EA AF: 0.372 AC: 3103

ExAC AF: 0.333 AC: 39664

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.22
DANN	Benign	0.35
DEOGEN2	Uncertain	0.58	D;D;D;D;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.15	.;.;.;T;T;T;T
MetaRNN	Benign	0.0000048	T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.39	N;N;N;N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N;.;.;N;N;.;N
REVEL	Benign	0.29
Sift	Benign	0.19	T;.;.;T;T;.;T
Sift4G	Benign	0.25	T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;.;B
Vest4		0.044
MPC		0.055
ClinPred		0.0055	T
GERP RS		-1.9
Varity_R		0.027
gMVP		0.56

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

Other links and lift over

dbSNP: rs8065080; hg19: chr17-3480447; COSMIC: COSV51518960; COSMIC: COSV51518960;