chr17-3566472-T-C

Variant names:

• chr17-3566472-T-C
• rs4790521
• NM_080704.4:c.*343A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018727.5(TRPV1):​c.*343A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 164,844 control chromosomes in the GnomAD database, including 8,653 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 0.32 (7930 hom., cov: 31)
  • Exomes 𝑓: 0.33 (723 hom.)
• Consequence: TRPV1 NM_018727.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.27
• Publications: 14 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018727.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	NM_080704.4	MANE Select	c.*343A>G		3_prime_UTR	Exon 17 of 17	NP_542435.2
	TRPV1	NM_018727.5		c.*343A>G		3_prime_UTR	Exon 16 of 16	NP_061197.4
	TRPV1	NM_080705.4		c.*343A>G		3_prime_UTR	Exon 16 of 16	NP_542436.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	ENST00000572705.2	TSL:1 MANE Select	c.*343A>G		3_prime_UTR	Exon 17 of 17	ENSP00000459962.1
	TRPV1	ENST00000399756.8	TSL:1	c.*343A>G		3_prime_UTR	Exon 15 of 15	ENSP00000382659.4
	TRPV1	ENST00000399759.7	TSL:1	c.*343A>G		3_prime_UTR	Exon 16 of 16	ENSP00000382661.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48946 AN: 151788 Hom.: 7922 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.329 AC: 4260 AN: 12940 Hom.: 723 Cov.: 0 AF XY: 0.327 AC XY: 2112 AN XY: 6468

African (AFR) AF: 0.344 AC: 207 AN: 602

American (AMR) AF: 0.230 AC: 100 AN: 434

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 171 AN: 616

East Asian (EAS) AF: 0.275 AC: 256 AN: 930

South Asian (SAS) AF: 0.265 AC: 43 AN: 162

European-Finnish (FIN) AF: 0.350 AC: 186 AN: 532

Middle Eastern (MID) AF: 0.375 AC: 21 AN: 56

European-Non Finnish (NFE) AF: 0.342 AC: 3003 AN: 8774

Other (OTH) AF: 0.327 AC: 273 AN: 834

GnomAD4 genome AF: 0.322 AC: 48981 AN: 151904 Hom.: 7930 Cov.: 31 AF XY: 0.317 AC XY: 23541 AN XY: 74214

African (AFR) AF: 0.340 AC: 14098 AN: 41404

American (AMR) AF: 0.270 AC: 4109 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1348 AN: 5182

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4818

European-Finnish (FIN) AF: 0.314 AC: 3309 AN: 10524

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22513 AN: 67958

Other (OTH) AF: 0.311 AC: 655 AN: 2104

Alfa AF: 0.309 Hom.: 932

Bravo AF: 0.317

Asia WGS AF: 0.264 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.30
PhyloP100		-4.3
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: rs4790521; hg19: chr17-3469766;