rs402369

Positions:

• chr17-3566107-A-G
• chr17-3566107-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.*708T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 151,800 control chromosomes in the GnomAD database, including 67,158 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 0.94 (67106 hom., cov: 27)
  • Exomes 𝑓: 0.99 (52 hom.)
• Consequence: TRPV1 NM_080704.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.*708T>C		3_prime_UTR_variant	17/17	ENST00000572705.2
TRPV1	NM_018727.5	c.*708T>C		3_prime_UTR_variant	16/16
TRPV1	NM_080705.4	c.*708T>C		3_prime_UTR_variant	16/16
TRPV1	NM_080706.3	c.*708T>C		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.*708T>C		3_prime_UTR_variant	17/17	1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.940 AC: 142447 AN: 151576 Hom.: 67052 Cov.: 27

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.962

GnomAD4 exome AF: 0.991 AC: 105 AN: 106 Hom.: 52 Cov.: 0 AF XY: 1.00 AC XY: 76 AN XY: 76

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.988

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.940 AC: 142559 AN: 151694 Hom.: 67106 Cov.: 27 AF XY: 0.942 AC XY: 69785 AN XY: 74090

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.954

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.962

Alfa AF: 0.946 Hom.: 8463

Bravo AF: 0.937

Asia WGS AF: 0.961 AC: 3343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.45

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: rs402369; hg19: chr17-3469401;