rs161365

Variant names:

• chr17-3580183-T-C
• rs161365
• NM_080704.4:c.1547+274A>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.1547+274A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,082 control chromosomes in the GnomAD database, including 34,787 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 0.67 (34787 hom., cov: 32)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.1547+274A>G		intron_variant	Intron 11 of 16	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.1547+274A>G		intron_variant	Intron 10 of 15		NP_061197.4
TRPV1	NM_080705.4	c.1547+274A>G		intron_variant	Intron 10 of 15		NP_542436.2
TRPV1	NM_080706.3	c.1547+274A>G		intron_variant	Intron 9 of 14		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.1547+274A>G		intron_variant	Intron 11 of 16	1	NM_080704.4	ENSP00000459962.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102181 AN: 151964 Hom.: 34748 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.673 AC: 102280 AN: 152082 Hom.: 34787 Cov.: 32 AF XY: 0.676 AC XY: 50228 AN XY: 74344

African (AFR) AF: 0.569 AC: 23600 AN: 41466

American (AMR) AF: 0.685 AC: 10465 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2662 AN: 3472

East Asian (EAS) AF: 0.828 AC: 4285 AN: 5174

South Asian (SAS) AF: 0.700 AC: 3376 AN: 4820

European-Finnish (FIN) AF: 0.694 AC: 7335 AN: 10574

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48205 AN: 67988

Other (OTH) AF: 0.687 AC: 1451 AN: 2112

Alfa AF: 0.708 Hom.: 22264

Bravo AF: 0.669

Asia WGS AF: 0.784 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.13
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: rs161365; hg19: chr17-3483477; COSMIC: COSV51523691; COSMIC: COSV51523691;