rs4790522

chr17-3566559-A-C

Variant summary

Our verdict is Benign. Variant got -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

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 (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/exons	MANE	UniProt
TRPV1	NM_080704.4	c.*256T>G		3_prime_UTR_variant	17/17	ENST00000572705.2
TRPV1	NM_018727.5	c.*256T>G		3_prime_UTR_variant	16/16
TRPV1	NM_080705.4	c.*256T>G		3_prime_UTR_variant	16/16
TRPV1	NM_080706.3	c.*256T>G		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.*256T>G		3_prime_UTR_variant	17/17	1	NM_080704.4	P1

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

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.603

Gnomad4 EAS exome AF: 0.732

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.581

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

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.573

Alfa AF: 0.565 Hom.: 35861

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

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: rs4790522; hg19: chr17-3469853;