rs222745

Variant names:

• chr17-3585577-G-A
• rs222745
• ENST00000572919.1:n.*2858C>T

Variant summary

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

The ENST00000572919.1(ENSG00000262304):​n.*2858C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 673,764 control chromosomes in the GnomAD database, including 6,463 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 0.099 (980 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5483 hom.)
• Consequence: ENSG00000262304 ENST00000572919.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 5 publications found

Genes affected

ENSG00000262304 (HGNC:):

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.1383+191C>T		intron_variant	Intron 9 of 16	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.1383+191C>T		intron_variant	Intron 8 of 15		NP_061197.4
TRPV1	NM_080705.4	c.1383+191C>T		intron_variant	Intron 8 of 15		NP_542436.2
TRPV1	NM_080706.3	c.1383+191C>T		intron_variant	Intron 7 of 14		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000262304	ENST00000572919.1	n.*2858C>T		non_coding_transcript_exon_variant	Exon 14 of 14	5		ENSP00000461416.1
ENSG00000262304	ENST00000572919.1	n.*2858C>T		3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000461416.1
TRPV1	ENST00000572705.2	c.1383+191C>T		intron_variant	Intron 9 of 16	1	NM_080704.4	ENSP00000459962.1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15081 AN: 152088 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.132 AC: 68734 AN: 521558 Hom.: 5483 Cov.: 7 AF XY: 0.136 AC XY: 36853 AN XY: 270492

African (AFR) AF: 0.0230 AC: 316 AN: 13740

American (AMR) AF: 0.137 AC: 2579 AN: 18820

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 1650 AN: 13850

East Asian (EAS) AF: 0.281 AC: 8575 AN: 30468

South Asian (SAS) AF: 0.224 AC: 10436 AN: 46500

European-Finnish (FIN) AF: 0.110 AC: 3130 AN: 28432

Middle Eastern (MID) AF: 0.102 AC: 213 AN: 2098

European-Non Finnish (NFE) AF: 0.113 AC: 38324 AN: 339602

Other (OTH) AF: 0.125 AC: 3511 AN: 28048

GnomAD4 genome AF: 0.0991 AC: 15086 AN: 152206 Hom.: 980 Cov.: 32 AF XY: 0.102 AC XY: 7617 AN XY: 74400

African (AFR) AF: 0.0260 AC: 1079 AN: 41558

American (AMR) AF: 0.122 AC: 1865 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3468

East Asian (EAS) AF: 0.259 AC: 1330 AN: 5144

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4820

European-Finnish (FIN) AF: 0.110 AC: 1172 AN: 10612

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7701 AN: 67996

Other (OTH) AF: 0.108 AC: 228 AN: 2116

Alfa AF: 0.106 Hom.: 1153

Bravo AF: 0.0941

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		0.13
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: rs222745; hg19: chr17-3488871;