rs224546

Variant names:

• chr17-3569577-T-C
• rs224546
• NM_080704.4:c.2347+1947A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.2347+1947A>G		intron_variant	Intron 16 of 16	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.2347+1947A>G		intron_variant	Intron 15 of 15		NP_061197.4
TRPV1	NM_080705.4	c.2347+1947A>G		intron_variant	Intron 15 of 15		NP_542436.2
TRPV1	NM_080706.3	c.2347+1947A>G		intron_variant	Intron 14 of 14		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.2347+1947A>G		intron_variant	Intron 16 of 16	1	NM_080704.4	ENSP00000459962.1

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

African (AFR) AF: 0.104 AC: 4302 AN: 41536

American (AMR) AF: 0.352 AC: 5368 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1293 AN: 5176

South Asian (SAS) AF: 0.445 AC: 2145 AN: 4820

European-Finnish (FIN) AF: 0.430 AC: 4547 AN: 10572

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.432 AC: 29374 AN: 67992

Other (OTH) AF: 0.351 AC: 740 AN: 2110

Alfa AF: 0.393 Hom.: 41267

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
PhyloP100		-0.089
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs224546; hg19: chr17-3472871;