rs4790522

Variant names:

• chr17-3566559-A-C
• rs4790522
• NM_080704.4:c.*256T>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.*256T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 389,250 control chromosomes in the GnomAD database, including 66,035 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 0.56 (23831 hom., cov: 32)
  • Exomes 𝑓: 0.59 (42204 hom.)
• Consequence: TRPV1 NM_080704.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 33 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 (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.*256T>G		3_prime_UTR_variant	Exon 17 of 17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.*256T>G		3_prime_UTR_variant	Exon 16 of 16		NP_061197.4
TRPV1	NM_080705.4	c.*256T>G		3_prime_UTR_variant	Exon 16 of 16		NP_542436.2
TRPV1	NM_080706.3	c.*256T>G		3_prime_UTR_variant	Exon 15 of 15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.*256T>G		3_prime_UTR_variant	Exon 17 of 17	1	NM_080704.4	ENSP00000459962.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84373 AN: 151958 Hom.: 23827 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.576

GnomAD4 exome AF: 0.591 AC: 140095 AN: 237174 Hom.: 42204 Cov.: 3 AF XY: 0.589 AC XY: 71136 AN XY: 120706

African (AFR) AF: 0.471 AC: 3621 AN: 7684

American (AMR) AF: 0.605 AC: 5329 AN: 8812

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 5126 AN: 8504

East Asian (EAS) AF: 0.732 AC: 13804 AN: 18862

South Asian (SAS) AF: 0.539 AC: 5011 AN: 9300

European-Finnish (FIN) AF: 0.649 AC: 10710 AN: 16502

Middle Eastern (MID) AF: 0.540 AC: 646 AN: 1196

European-Non Finnish (NFE) AF: 0.576 AC: 86923 AN: 150940

Other (OTH) AF: 0.581 AC: 8925 AN: 15374

GnomAD4 genome AF: 0.555 AC: 84420 AN: 152076 Hom.: 23831 Cov.: 32 AF XY: 0.559 AC XY: 41551 AN XY: 74344

African (AFR) AF: 0.467 AC: 19374 AN: 41470

American (AMR) AF: 0.600 AC: 9162 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3754 AN: 5168

South Asian (SAS) AF: 0.536 AC: 2580 AN: 4814

European-Finnish (FIN) AF: 0.650 AC: 6884 AN: 10590

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38700 AN: 67966

Other (OTH) AF: 0.573 AC: 1208 AN: 2110

Alfa AF: 0.565 Hom.: 49315

Bravo AF: 0.549

Asia WGS AF: 0.620 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.48
PhyloP100		-2.2
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: rs4790522; hg19: chr17-3469853;