rs224547

Positions:

• chr17-3571724-A-G
• chr17-3571724-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.2232-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,092,720 control chromosomes in the GnomAD database, including 103,504 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 0.35 (10983 hom., cov: 32)
  • Exomes 𝑓: 0.44 (92521 hom.)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.2232-85T>C		intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.2232-85T>C		intron_variant
TRPV1	NM_080705.4	c.2232-85T>C		intron_variant
TRPV1	NM_080706.3	c.2232-85T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.2232-85T>C		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52787 AN: 151794 Hom.: 10981 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.437 AC: 411012 AN: 940806 Hom.: 92521 AF XY: 0.439 AC XY: 209549 AN XY: 477448

Gnomad4 AFR exome AF: 0.0940

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.439

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.348 AC: 52800 AN: 151914 Hom.: 10983 Cov.: 32 AF XY: 0.351 AC XY: 26038 AN XY: 74228

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.388

Alfa AF: 0.425 Hom.: 4282

Bravo AF: 0.329

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs224547; hg19: chr17-3475018; COSMIC: COSV51516372; COSMIC: COSV51516372;