chr17-3570651-T-G

Variant names:

• chr17-3570651-T-G
• rs11655540
• NM_080704.4:c.2347+873A>C

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+873A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,088 control chromosomes in the GnomAD database, including 6,221 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 0.28 (6221 hom., cov: 32)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.2347+873A>C		intron_variant	Intron 16 of 16	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.2347+873A>C		intron_variant	Intron 15 of 15		NP_061197.4
TRPV1	NM_080705.4	c.2347+873A>C		intron_variant	Intron 15 of 15		NP_542436.2
TRPV1	NM_080706.3	c.2347+873A>C		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+873A>C		intron_variant	Intron 16 of 16	1	NM_080704.4	ENSP00000459962.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42648 AN: 151970 Hom.: 6222 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.280 AC: 42656 AN: 152088 Hom.: 6221 Cov.: 32 AF XY: 0.276 AC XY: 20506 AN XY: 74352

African (AFR) AF: 0.212 AC: 8788 AN: 41482

American (AMR) AF: 0.309 AC: 4720 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3468

East Asian (EAS) AF: 0.153 AC: 791 AN: 5182

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2981 AN: 10566

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21978 AN: 67988

Other (OTH) AF: 0.275 AC: 579 AN: 2108

Alfa AF: 0.307 Hom.: 19484

Bravo AF: 0.276

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.79
PhyloP100		0.43
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: rs11655540; hg19: chr17-3473945;