rs3826503

chr17-3571366-G-A

Variant summary

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

The NM_080704.4(TRPV1):c.2347+158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,174 control chromosomes in the GnomAD database, including 2,874 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 0.18 (2874 hom., cov: 33)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.2347+158C>T		intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.2347+158C>T		intron_variant
TRPV1	NM_080705.4	c.2347+158C>T		intron_variant
TRPV1	NM_080706.3	c.2347+158C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.2347+158C>T		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26740 AN: 152054 Hom.: 2873 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.176 AC: 26765 AN: 152174 Hom.: 2874 Cov.: 33 AF XY: 0.184 AC XY: 13660 AN XY: 74368

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.193

Alfa AF: 0.172 Hom.: 2122

Bravo AF: 0.175

Asia WGS AF: 0.366 AC: 1271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.23
Dann	Benign	0.68

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: rs3826503; hg19: chr17-3474660;