NM_080704.4:c.945G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080704.4(TRPV1):c.945G>C(p.Met315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,598,084 control chromosomes in the GnomAD database, including 452,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.77 ( 45571 hom., cov: 32)

Exomes 𝑓: 0.75 ( 407424 hom. )

Consequence

TRPV1
NM_080704.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

Publications

90 publications found

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:

ENSG00000262304 (HGNC:):

ENSG00000262304 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.156609E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.945G>C	p.Met315Ile	missense_variant	Exon 7 of 17	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.945G>C	p.Met315Ile	missense_variant	Exon 6 of 16		NP_061197.4	Q8NER1-1
TRPV1	NM_080705.4 link	c.945G>C	p.Met315Ile	missense_variant	Exon 6 of 16		NP_542436.2	Q8NER1-1
TRPV1	NM_080706.3 link	c.945G>C	p.Met315Ile	missense_variant	Exon 5 of 15		NP_542437.2	Q8NER1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPV1	ENST00000572705.2 link	c.945G>C	p.Met315Ile	missense_variant	Exon 7 of 17	1	NM_080704.4	ENSP00000459962.1	Q8NER1-1
ENSG00000262304	ENST00000572919.1 link	n.*2229G>C		non_coding_transcript_exon_variant	Exon 12 of 14	5		ENSP00000461416.1	A0A0B4J2A0
ENSG00000262304	ENST00000572919.1 link	n.*2229G>C		3_prime_UTR_variant	Exon 12 of 14	5		ENSP00000461416.1	A0A0B4J2A0

Frequencies

GnomAD3 genomes

AF:

0.768

AC:

116758

AN:

152004

Hom.:

45546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.879

Gnomad AMI

AF:

0.816

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.767

GnomAD2 exomes

AF:

0.723

AC:

159239

AN:

220190

AF XY:

0.725

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.733

Gnomad ASJ exome

AF:

0.735

Gnomad EAS exome

AF:

0.427

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.748

Gnomad OTH exome

AF:

0.732

GnomAD4 exome

AF:

0.748

AC:

1081985

AN:

1445960

Hom.:

407424

Cov.:

AF XY:

0.748

AC XY:

536803

AN XY:

717920

show subpopulations

African (AFR)

AF:

0.890

AC:

29417

AN:

33064

American (AMR)

AF:

0.737

AC:

30757

AN:

41736

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

18931

AN:

25776

East Asian (EAS)

AF:

0.480

AC:

18599

AN:

38742

South Asian (SAS)

AF:

0.760

AC:

63655

AN:

83810

European-Finnish (FIN)

AF:

0.661

AC:

34702

AN:

52462

Middle Eastern (MID)

AF:

0.767

AC:

4414

AN:

5756

European-Non Finnish (NFE)

AF:

0.758

AC:

836998

AN:

1104768

Other (OTH)

AF:

0.744

AC:

44512

AN:

59846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

17955

35910

53864

71819

89774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20290

40580

60870

81160

101450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.768

AC:

116832

AN:

152124

Hom.:

45571

Cov.:

AF XY:

0.760

AC XY:

56497

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.879

AC:

36480

AN:

41522

American (AMR)

AF:

0.740

AC:

11297

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.738

AC:

2561

AN:

3472

East Asian (EAS)

AF:

0.434

AC:

2230

AN:

5144

South Asian (SAS)

AF:

0.754

AC:

3632

AN:

4816

European-Finnish (FIN)

AF:

0.645

AC:

6823

AN:

10578

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.753

AC:

51208

AN:

68002

Other (OTH)

AF:

0.763

AC:

1612

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1345

2690

4036

5381

6726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.746

Hom.:

32124

Bravo

AF:

0.775

TwinsUK

AF:

0.751

AC:

2783

ALSPAC

AF:

0.758

AC:

2923

ESP6500AA

AF:

0.884

AC:

3764

ESP6500EA

AF:

0.762

AC:

6471

ExAC

AF:

0.712

AC:

85744

Asia WGS

AF:

0.631

AC:

2197

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.24

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.027

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

MetaRNN

Benign

6.2e-7

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.6

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

PhyloP100

0.81

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.1

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

REVEL

Benign

0.066

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.10

MutPred

0.41

Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);Gain of catalytic residue at M315 (P = 0.0678);

MPC

0.070

ClinPred

0.0015

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.29

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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