NM_080704.4:c.501C>T

Variant names:

• chr17-3591067-G-A
• rs222748
• NM_080704.4:c.501C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_080704.4(TRPV1):​c.501C>T​(p.His167His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,612,620 control chromosomes in the GnomAD database, including 13,651 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 0.10 (1000 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12651 hom.)
• Consequence: TRPV1 NM_080704.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• Publications: 24 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]

ENSG00000262304 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-0.727 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.501C>T	p.His167His	synonymous_variant	Exon 5 of 17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.501C>T	p.His167His	synonymous_variant	Exon 4 of 16		NP_061197.4
TRPV1	NM_080705.4	c.501C>T	p.His167His	synonymous_variant	Exon 4 of 16		NP_542436.2
TRPV1	NM_080706.3	c.501C>T	p.His167His	synonymous_variant	Exon 3 of 15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.501C>T	p.His167His	synonymous_variant	Exon 5 of 17	1	NM_080704.4	ENSP00000459962.1
ENSG00000262304	ENST00000572919.1	n.*1785C>T		non_coding_transcript_exon_variant	Exon 10 of 14	5		ENSP00000461416.1
ENSG00000262304	ENST00000572919.1	n.*1785C>T		3_prime_UTR_variant	Exon 10 of 14	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15792 AN: 152088 Hom.: 998 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.136 AC: 33621 AN: 246538 AF XY: 0.139

Gnomad AFR exome AF: 0.0365

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.241

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.125 AC: 181881 AN: 1460414 Hom.: 12651 Cov.: 34 AF XY: 0.127 AC XY: 92205 AN XY: 726360

African (AFR) AF: 0.0368 AC: 1233 AN: 33468

American (AMR) AF: 0.141 AC: 6264 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3186 AN: 26096

East Asian (EAS) AF: 0.265 AC: 10512 AN: 39654

South Asian (SAS) AF: 0.222 AC: 19119 AN: 85952

European-Finnish (FIN) AF: 0.123 AC: 6565 AN: 53346

Middle Eastern (MID) AF: 0.136 AC: 781 AN: 5740

European-Non Finnish (NFE) AF: 0.114 AC: 126561 AN: 1111386

Other (OTH) AF: 0.127 AC: 7660 AN: 60346

GnomAD4 genome AF: 0.104 AC: 15802 AN: 152206 Hom.: 1000 Cov.: 32 AF XY: 0.107 AC XY: 7993 AN XY: 74424

African (AFR) AF: 0.0415 AC: 1723 AN: 41534

American (AMR) AF: 0.126 AC: 1931 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1290 AN: 5166

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4824

European-Finnish (FIN) AF: 0.121 AC: 1280 AN: 10608

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7690 AN: 67994

Other (OTH) AF: 0.109 AC: 231 AN: 2112

Alfa AF: 0.0997 Hom.: 1046

Bravo AF: 0.0984

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs222748; hg19: chr17-3494361; COSMIC: COSV51518497;