rs224546

Positions:

• chr17-3569577-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.2347+1947A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,146 control chromosomes in the GnomAD database, including 9,654 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 0.33 (9654 hom., cov: 33)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.2347+1947A>G		intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.2347+1947A>G		intron_variant
TRPV1	NM_080705.4	c.2347+1947A>G		intron_variant
TRPV1	NM_080706.3	c.2347+1947A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.2347+1947A>G		intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49557 AN: 152028 Hom.: 9653 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49570 AN: 152146 Hom.: 9654 Cov.: 33 AF XY: 0.329 AC XY: 24463 AN XY: 74370

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.351

Alfa AF: 0.414 Hom.: 27574

Bravo AF: 0.306

Asia WGS AF: 0.336 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.5
DANN	Benign	0.63

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: rs224546; hg19: chr17-3472871;