Variant chr17-3571563-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080704.4(TRPV1):c.2308G>T(p.Val770Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,502 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.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRPV1
NM_080704.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.908

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.109855354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.2308G>T	p.Val770Phe	missense_variant	Exon 16 of 17	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.2308G>T	p.Val770Phe	missense_variant	Exon 15 of 16		NP_061197.4	Q8NER1-1
TRPV1	NM_080705.4 link	c.2308G>T	p.Val770Phe	missense_variant	Exon 15 of 16		NP_542436.2	Q8NER1-1
TRPV1	NM_080706.3 link	c.2308G>T	p.Val770Phe	missense_variant	Exon 14 of 15		NP_542437.2	Q8NER1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2 link	c.2308G>T	p.Val770Phe	missense_variant	Exon 16 of 17	1	NM_080704.4	ENSP00000459962.1		Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00000408

AC:

AN:

244942

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132810

show subpopulations

Gnomad AFR exome

AF:

0.0000661

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:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459280

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

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

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.065

MetaRNN

Benign

0.11

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

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.69

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

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

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

REVEL

Uncertain

0.31

Sift

Benign

0.095

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

Sift4G

Benign

0.34

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

Polyphen

0.0010

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

Vest4

0.25

MutPred

0.27

.;.;.;.;Gain of helix (P = 0.0225);.;.;

MVP

0.60

MPC

0.084

ClinPred

0.11

GERP RS

-0.20

Varity_R

0.064

gMVP

0.42

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