NM_080704.4:c.1753A>G

Variant names:

• chr17-3577153-T-C
• rs8065080
• NM_080704.4:c.1753A>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 136 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080704.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	NM_080704.4	MANE Select	c.1753A>G	p.Ile585Val	missense	Exon 13 of 17	NP_542435.2	Q8NER1-1
	TRPV1	NM_018727.5		c.1753A>G	p.Ile585Val	missense	Exon 12 of 16	NP_061197.4	Q8NER1-1
	TRPV1	NM_080705.4		c.1753A>G	p.Ile585Val	missense	Exon 12 of 16	NP_542436.2	Q8NER1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	ENST00000572705.2	TSL:1 MANE Select	c.1753A>G	p.Ile585Val	missense	Exon 13 of 17	ENSP00000459962.1	Q8NER1-1
	TRPV1	ENST00000425167.6	TSL:1	c.1786A>G	p.Ile596Val	missense	Exon 12 of 16	ENSP00000409627.2	E7EQ78
	TRPV1	ENST00000399756.8	TSL:1	c.1753A>G	p.Ile585Val	missense	Exon 11 of 15	ENSP00000382659.4	Q8NER1-1

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

GnomAD2 exomes AF: 0.368 AC: 77537 AN: 210474 AF XY: 0.367

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 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

African (AFR) AF: 0.137 AC: 4499 AN: 32910

American (AMR) AF: 0.318 AC: 12880 AN: 40444

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 11939 AN: 25620

East Asian (EAS) AF: 0.636 AC: 24443 AN: 38412

South Asian (SAS) AF: 0.264 AC: 21607 AN: 81936

European-Finnish (FIN) AF: 0.431 AC: 22243 AN: 51580

Middle Eastern (MID) AF: 0.386 AC: 2214 AN: 5742

European-Non Finnish (NFE) AF: 0.377 AC: 414537 AN: 1099104

Other (OTH) AF: 0.373 AC: 22226 AN: 59556

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

African (AFR) AF: 0.145 AC: 5995 AN: 41450

American (AMR) AF: 0.339 AC: 5185 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3470

East Asian (EAS) AF: 0.594 AC: 3058 AN: 5148

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4816

European-Finnish (FIN) AF: 0.455 AC: 4800 AN: 10538

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25774 AN: 67962

Other (OTH) AF: 0.356 AC: 750 AN: 2106

Alfa AF: 0.371 Hom.: 47432

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 v4.9

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
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0000048	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.39	N
PhyloP100		-0.23
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.29
Sift	Benign	0.19	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.044
MPC		0.055
ClinPred		0.0055	T
GERP RS		-1.9
Varity_R		0.027
gMVP		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

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