rs222749

Positions:

• chr17-3592080-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080704.4(TRPV1):​c.271C>T​(p.Pro91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,611,674 control chromosomes in the GnomAD database, including 4,157 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.050 (340 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3817 hom.)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038556755).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.271C>T	p.Pro91Ser	missense_variant	3/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.271C>T	p.Pro91Ser	missense_variant	2/16		NP_061197.4
TRPV1	NM_080705.4	c.271C>T	p.Pro91Ser	missense_variant	2/16		NP_542436.2
TRPV1	NM_080706.3	c.271C>T	p.Pro91Ser	missense_variant	1/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.271C>T	p.Pro91Ser	missense_variant	3/17	1	NM_080704.4	ENSP00000459962.1
ENSG00000262304	ENST00000572919.1	n.*1555C>T		non_coding_transcript_exon_variant	8/14	5		ENSP00000461416.1
ENSG00000262304	ENST00000572919.1	n.*1555C>T		3_prime_UTR_variant	8/14	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7630 AN: 152102 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0991

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0518

Gnomad OTH AF: 0.0603

GnomAD3 exomes AF: 0.0743 AC: 18287 AN: 246222 Hom.: 1126 AF XY: 0.0731 AC XY: 9785 AN XY: 133906

Gnomad AFR exome AF: 0.00862

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.0216

Gnomad EAS exome AF: 0.239

Gnomad SAS exome AF: 0.0972

Gnomad FIN exome AF: 0.0325

Gnomad NFE exome AF: 0.0507

Gnomad OTH exome AF: 0.0568

GnomAD4 exome AF: 0.0597 AC: 87107 AN: 1459454 Hom.: 3817 Cov.: 32 AF XY: 0.0601 AC XY: 43616 AN XY: 725650

Gnomad4 AFR exome AF: 0.00861

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.0934

Gnomad4 FIN exome AF: 0.0341

Gnomad4 NFE exome AF: 0.0519

Gnomad4 OTH exome AF: 0.0613

GnomAD4 genome AF: 0.0502 AC: 7649 AN: 152220 Hom.: 340 Cov.: 32 AF XY: 0.0522 AC XY: 3884 AN XY: 74404

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.0288

Gnomad4 NFE AF: 0.0518

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0551 Hom.: 740

Bravo AF: 0.0536

TwinsUK AF: 0.0539 AC: 200

ALSPAC AF: 0.0592 AC: 228

ESP6500AA AF: 0.00965 AC: 39

ESP6500EA AF: 0.0494 AC: 412

ExAC AF: 0.0717 AC: 8677

Asia WGS AF: 0.182 AC: 631 AN: 3478

EpiCase AF: 0.0468

EpiControl AF: 0.0455

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;T;T;T;.;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.83	.;.;.;T;T;T;T
MetaRNN	Benign	0.0039	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L;L;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N;.;.;N;N;.;N
REVEL	Benign	0.12
Sift	Benign	0.17	T;.;.;T;T;.;T
Sift4G	Benign	0.18	T;T;T;T;T;T;T
Polyphen		0.18	B;B;B;B;P;.;B
Vest4		0.068
MPC		0.065
ClinPred		0.0065	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.055
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs222749; hg19: chr17-3495374; COSMIC: COSV51516383;