rs11655540

Positions:

• chr17-3570651-T-G

Variant summary

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

The NM_080704.4(TRPV1):​c.2347+873A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,088 control chromosomes in the GnomAD database, including 6,221 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 0.28 (6221 hom., cov: 32)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.2347+873A>C		intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.2347+873A>C		intron_variant
TRPV1	NM_080705.4	c.2347+873A>C		intron_variant
TRPV1	NM_080706.3	c.2347+873A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.2347+873A>C		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42648 AN: 151970 Hom.: 6222 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.280 AC: 42656 AN: 152088 Hom.: 6221 Cov.: 32 AF XY: 0.276 AC XY: 20506 AN XY: 74352

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.275

Alfa AF: 0.313 Hom.: 14280

Bravo AF: 0.276

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.79

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: rs11655540; hg19: chr17-3473945;