rs2277675

Positions:

• chr17-3597216-T-C

Variant summary

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

The NM_080704.4(TRPV1):​c.-33-4833A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 155,618 control chromosomes in the GnomAD database, including 15,509 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 0.40 (15395 hom., cov: 32)
  • Exomes 𝑓: 0.24 (114 hom.)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.-33-4833A>G		intron_variant		ENST00000572705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.-33-4833A>G		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60343 AN: 151952 Hom.: 15358 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.240 AC: 850 AN: 3548 Hom.: 114 AF XY: 0.234 AC XY: 444 AN XY: 1898

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.397 AC: 60431 AN: 152070 Hom.: 15395 Cov.: 32 AF XY: 0.390 AC XY: 29006 AN XY: 74344

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.376

Alfa AF: 0.281 Hom.: 12897

Bravo AF: 0.420

Asia WGS AF: 0.240 AC: 834 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	3.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2277675; hg19: chr17-3500510;