rs222738

chr17-3601921-C-T

Variant summary

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

The NM_080704.4(TRPV1):c.-34+6506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 152,194 control chromosomes in the GnomAD database, including 739 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 0.088 (739 hom., cov: 30)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

(HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.-34+6506G>A		intron_variant		ENST00000572705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.-34+6506G>A		intron_variant		1	NM_080704.4	P1
	ENST00000575593.1	n.352G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13327 AN: 152062 Hom.: 734 Cov.: 30

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0875

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0847

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

GnomAD4 genome AF: 0.0877 AC: 13350 AN: 152180 Hom.: 739 Cov.: 30 AF XY: 0.0909 AC XY: 6760 AN XY: 74400

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0875

Gnomad4 NFE AF: 0.0986

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.100 Hom.: 446

Bravo AF: 0.0840

Asia WGS AF: 0.282 AC: 983 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	0.41
Dann	Benign	0.75

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: rs222738; hg19: chr17-3505215;