17-3596159-G-C

Variant names:

• chr17-3596159-G-C
• rs10491215
• NM_080704.4:c.-33-3776C>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.-33-3776C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,146 control chromosomes in the GnomAD database, including 6,280 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 0.16 (6280 hom., cov: 32)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 1 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]

ENSG00000262304 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.-33-3776C>G		intron_variant	Intron 2 of 16	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.-34+759C>G		intron_variant	Intron 1 of 15		NP_061197.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.-33-3776C>G		intron_variant	Intron 2 of 16	1	NM_080704.4	ENSP00000459962.1
TRPV1	ENST00000571088.5	c.-34+759C>G		intron_variant	Intron 1 of 15	1		ENSP00000461007.1
ENSG00000262304	ENST00000572919.1	n.*1252-3776C>G		intron_variant	Intron 7 of 13	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24182 AN: 152026 Hom.: 6261 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.159 AC: 24247 AN: 152146 Hom.: 6280 Cov.: 32 AF XY: 0.154 AC XY: 11481 AN XY: 74398

African (AFR) AF: 0.546 AC: 22617 AN: 41440

American (AMR) AF: 0.0660 AC: 1009 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3468

East Asian (EAS) AF: 0.0233 AC: 121 AN: 5184

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00266 AC: 181 AN: 67998

Other (OTH) AF: 0.114 AC: 241 AN: 2116

Alfa AF: 0.0231 Hom.: 99

Bravo AF: 0.184

Asia WGS AF: 0.0450 AC: 157 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	4.1
DANN	Benign	0.44
PhyloP100		-0.034
PromoterAI		-0.015	Neutral
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: rs10491215; hg19: chr17-3499453;