17-3577139-G-C

Position:

chr17-3577139-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000572705.2(TRPV1):c.1767C>G(p.Phe589Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,586,946 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00094 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 3 hom. )

Consequence

TRPV1
ENST00000572705.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.650

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01849866).

BP6

Variant 17-3577139-G-C is Benign according to our data. Variant chr17-3577139-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 773586.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPV1	NM_080704.4 linkuse as main transcript	c.1767C>G	p.Phe589Leu	missense_variant	13/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5 linkuse as main transcript	c.1767C>G	p.Phe589Leu	missense_variant	12/16		NP_061197.4
TRPV1	NM_080705.4 linkuse as main transcript	c.1767C>G	p.Phe589Leu	missense_variant	12/16		NP_542436.2
TRPV1	NM_080706.3 linkuse as main transcript	c.1767C>G	p.Phe589Leu	missense_variant	11/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2 linkuse as main transcript	c.1767C>G	p.Phe589Leu	missense_variant	13/17	1	NM_080704.4	ENSP00000459962	P1	Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000927

AC:

193

AN:

208094

Hom.:

AF XY:

0.000850

AC XY:

AN XY:

111746

show subpopulations

Gnomad AFR exome

AF:

0.000414

Gnomad AMR exome

AF:

0.000981

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000704

Gnomad FIN exome

AF:

0.000312

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.000557

GnomAD4 exome

AF:

0.00162

AC:

2320

AN:

1434704

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1093

AN XY:

710978

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000978

Gnomad4 FIN exome

AF:

0.000310

Gnomad4 NFE exome

AF:

0.00191

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152242

Hom.:

Cov.:

AF XY:

0.000941

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.0000641

Hom.:

Bravo

AF:

0.000963

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00144

AC:

ExAC

AF:

0.000865

AC:

104

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Benign

1.1

DANN

Benign

0.87

DEOGEN2

Uncertain

0.70

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.84

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

M_CAP

Benign

0.027

MetaRNN

Benign

0.018

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.13

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

MutationTaster

Benign

0.97

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

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

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

REVEL

Uncertain

0.40

Sift

Benign

0.54

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

Sift4G

Benign

1.0

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

Polyphen

0.011

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

Vest4

0.25

MutPred

0.47

.;.;.;.;Loss of catalytic residue at G601 (P = 0.1562);.;.;

MVP

0.21

MPC

0.074

ClinPred

0.013

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over