Variant 17-3591067-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_080704.4(TRPV1):c.501C>A(p.His167Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H167R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TRPV1
NM_080704.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.727

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03066963).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRPV1	NM_080704.4 linkuse as main transcript	c.501C>A	p.His167Gln	missense_variant	5/17	ENST00000572705.2
TRPV1	NM_018727.5 linkuse as main transcript	c.501C>A	p.His167Gln	missense_variant	4/16
TRPV1	NM_080705.4 linkuse as main transcript	c.501C>A	p.His167Gln	missense_variant	4/16
TRPV1	NM_080706.3 linkuse as main transcript	c.501C>A	p.His167Gln	missense_variant	3/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2 linkuse as main transcript	c.501C>A	p.His167Gln	missense_variant	5/17	1	NM_080704.4	P1	Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000243

AC:

AN:

246538

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133750

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460564

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000461

Hom.:

796

ExAC

AF:

0.0000495

AC:

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

Benign

-0.35

CADD

Benign

0.23

DANN

Benign

0.37

DEOGEN2

Benign

0.25

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

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.70

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

M_CAP

Benign

0.023

MetaRNN

Benign

0.031

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

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-0.12

N;N;N;N;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;.;.;N;N;.;N

REVEL

Uncertain

0.33

Sift

Benign

0.28

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

Sift4G

Benign

0.54

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

Polyphen

0.0010

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

Vest4

0.16

MutPred

0.37

Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);

MVP

0.19

MPC

0.065

ClinPred

0.032

GERP RS

-9.0

Varity_R

0.21

gMVP

0.50

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

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