rs4790523

chr17-3567183-C-Achr17-3567183-C-T

Variant summary

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

The NM_080704.4(TRPV1):c.2348-196G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 148,376 control chromosomes in the GnomAD database, including 3,278 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 0.19 (3278 hom., cov: 26)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.2348-196G>T		intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.2348-196G>T		intron_variant
TRPV1	NM_080705.4	c.2348-196G>T		intron_variant
TRPV1	NM_080706.3	c.2348-196G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.2348-196G>T		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 28454 AN: 148266 Hom.: 3279 Cov.: 26

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 28456 AN: 148376 Hom.: 3278 Cov.: 26 AF XY: 0.200 AC XY: 14442 AN XY: 72182

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.214

Alfa AF: 0.102 Hom.: 162

Bravo AF: 0.198

Asia WGS AF: 0.350 AC: 1216 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.70
Dann	Benign	0.35

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: rs4790523; hg19: chr17-3470477; COSMIC: COSV51523576;