17-3571724-A-G

Variant names:

• chr17-3571724-A-G
• rs224547
• NM_080704.4:c.2232-85T>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.2232-85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,092,720 control chromosomes in the GnomAD database, including 103,504 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 0.35 (10983 hom., cov: 32)
  • Exomes 𝑓: 0.44 (92521 hom.)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.2232-85T>C		intron_variant	Intron 15 of 16	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.2232-85T>C		intron_variant	Intron 14 of 15		NP_061197.4
TRPV1	NM_080705.4	c.2232-85T>C		intron_variant	Intron 14 of 15		NP_542436.2
TRPV1	NM_080706.3	c.2232-85T>C		intron_variant	Intron 13 of 14		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.2232-85T>C		intron_variant	Intron 15 of 16	1	NM_080704.4	ENSP00000459962.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52787 AN: 151794 Hom.: 10981 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.437 AC: 411012 AN: 940806 Hom.: 92521 AF XY: 0.439 AC XY: 209549 AN XY: 477448

African (AFR) AF: 0.0940 AC: 2140 AN: 22778

American (AMR) AF: 0.425 AC: 13527 AN: 31848

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 8665 AN: 20906

East Asian (EAS) AF: 0.246 AC: 8210 AN: 33320

South Asian (SAS) AF: 0.439 AC: 29929 AN: 68244

European-Finnish (FIN) AF: 0.446 AC: 21247 AN: 47602

Middle Eastern (MID) AF: 0.415 AC: 1911 AN: 4606

European-Non Finnish (NFE) AF: 0.460 AC: 307578 AN: 668964

Other (OTH) AF: 0.419 AC: 17805 AN: 42538

GnomAD4 genome AF: 0.348 AC: 52800 AN: 151914 Hom.: 10983 Cov.: 32 AF XY: 0.351 AC XY: 26038 AN XY: 74228

African (AFR) AF: 0.108 AC: 4460 AN: 41448

American (AMR) AF: 0.403 AC: 6152 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1448 AN: 3466

East Asian (EAS) AF: 0.250 AC: 1282 AN: 5138

South Asian (SAS) AF: 0.444 AC: 2134 AN: 4808

European-Finnish (FIN) AF: 0.449 AC: 4736 AN: 10558

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31219 AN: 67914

Other (OTH) AF: 0.388 AC: 817 AN: 2106

Alfa AF: 0.427 Hom.: 5028

Bravo AF: 0.329

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		-0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs224547; hg19: chr17-3475018; COSMIC: COSV51516372; COSMIC: COSV51516372;