rs16953163

chr17-3567945-A-Gchr17-3567945-A-T

Variant summary

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

The NM_080704.4(TRPV1):c.2348-958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,144 control chromosomes in the GnomAD database, including 2,842 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 0.17 (2842 hom., cov: 31)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.2348-958T>C		intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.2348-958T>C		intron_variant
TRPV1	NM_080705.4	c.2348-958T>C		intron_variant
TRPV1	NM_080706.3	c.2348-958T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.2348-958T>C		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25532 AN: 152026 Hom.: 2845 Cov.: 31

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.168 AC: 25527 AN: 152144 Hom.: 2842 Cov.: 31 AF XY: 0.176 AC XY: 13099 AN XY: 74356

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.184

Alfa AF: 0.189 Hom.: 3848

Bravo AF: 0.163

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.5
Dann	Benign	0.77

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: rs16953163; hg19: chr17-3471239; COSMIC: COSV51523597;