rs222745

Positions:

• chr17-3585577-G-A

Variant summary

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

The NM_080704.4(TRPV1):​c.1383+191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 673,764 control chromosomes in the GnomAD database, including 6,463 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 0.099 (980 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5483 hom.)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.1383+191C>T		intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.1383+191C>T		intron_variant
TRPV1	NM_080705.4	c.1383+191C>T		intron_variant
TRPV1	NM_080706.3	c.1383+191C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.1383+191C>T		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15081 AN: 152088 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.132 AC: 68734 AN: 521558 Hom.: 5483 Cov.: 7 AF XY: 0.136 AC XY: 36853 AN XY: 270492

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0991 AC: 15086 AN: 152206 Hom.: 980 Cov.: 32 AF XY: 0.102 AC XY: 7617 AN XY: 74400

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.108

Alfa AF: 0.110 Hom.: 930

Bravo AF: 0.0941

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
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: rs222745; hg19: chr17-3488871;