Variant 17-3583408-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000572705.2(TRPV1):c.1406C>T(p.Thr469Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,603,258 control chromosomes in the GnomAD database, including 112,346 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.31 ( 9156 hom., cov: 33)

Exomes 𝑓: 0.37 ( 103190 hom. )

Consequence

TRPV1
ENST00000572705.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Variant links:

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]

TRPV1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0098341E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPV1	NM_080704.4 linkuse as main transcript	c.1406C>T	p.Thr469Ile	missense_variant	10/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5 linkuse as main transcript	c.1406C>T	p.Thr469Ile	missense_variant	9/16		NP_061197.4
TRPV1	NM_080705.4 linkuse as main transcript	c.1406C>T	p.Thr469Ile	missense_variant	9/16		NP_542436.2
TRPV1	NM_080706.3 linkuse as main transcript	c.1406C>T	p.Thr469Ile	missense_variant	8/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2 linkuse as main transcript	c.1406C>T	p.Thr469Ile	missense_variant	10/17	1	NM_080704.4	ENSP00000459962	P1	Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46534

AN:

152086

Hom.:

9151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0805

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.394

AC:

92858

AN:

235758

Hom.:

20344

AF XY:

0.395

AC XY:

50279

AN XY:

127374

show subpopulations

Gnomad AFR exome

AF:

0.0709

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.771

Gnomad SAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.357

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.366

AC:

530538

AN:

1451054

Hom.:

103190

Cov.:

AF XY:

0.368

AC XY:

265019

AN XY:

720904

show subpopulations

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.392

Gnomad4 ASJ exome

AF:

0.386

Gnomad4 EAS exome

AF:

0.753

Gnomad4 SAS exome

AF:

0.418

Gnomad4 FIN exome

AF:

0.450

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.365

GnomAD4 genome

AF:

0.306

AC:

46546

AN:

152204

Hom.:

9156

Cov.:

AF XY:

0.316

AC XY:

23543

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0804

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.771

Gnomad4 SAS

AF:

0.433

Gnomad4 FIN

AF:

0.464

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.353

Hom.:

26319

Bravo

AF:

0.291

TwinsUK

AF:

0.362

AC:

1343

ALSPAC

AF:

0.347

AC:

1336

ESP6500AA

AF:

0.0852

AC:

325

ESP6500EA

AF:

0.344

AC:

2842

ExAC

AF:

0.377

AC:

45465

Asia WGS

AF:

0.608

AC:

2114

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.89

D;D;D;D;.;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.44

.;.;.;T;T;T;T

MetaRNN

Benign

0.0000020

T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.9

M;M;M;M;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.3

D;.;.;D;D;.;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.019

D;.;.;D;D;.;D

Sift4G

Uncertain

0.012

D;D;D;D;D;D;D

Polyphen

0.025

B;B;B;B;B;.;B

Vest4

0.15

MPC

0.074

ClinPred

0.017

GERP RS

4.1

Varity_R

0.094

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over