rs222749

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.271C>T(p.Pro91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,611,674 control chromosomes in the GnomAD database, including 4,157 homozygotes. 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 0.050 ( 340 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3817 hom. )

Consequence

TRPV1
NM_080704.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.542

Publications

39 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=0.0038556755).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 3 of 17	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 2 of 16		NP_061197.4	Q8NER1-1
TRPV1	NM_080705.4 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 2 of 16		NP_542436.2	Q8NER1-1
TRPV1	NM_080706.3 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 1 of 15		NP_542437.2	Q8NER1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPV1	ENST00000572705.2 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 3 of 17	1	NM_080704.4	ENSP00000459962.1	Q8NER1-1
ENSG00000262304	ENST00000572919.1 link	n.*1555C>T		non_coding_transcript_exon_variant	Exon 8 of 14	5		ENSP00000461416.1	A0A0B4J2A0
ENSG00000262304	ENST00000572919.1 link	n.*1555C>T		3_prime_UTR_variant	Exon 8 of 14	5		ENSP00000461416.1	A0A0B4J2A0

Frequencies

GnomAD3 genomes

AF:

0.0502

AC:

7630

AN:

152102

Hom.:

336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0900

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.0991

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0518

Gnomad OTH

AF:

0.0603

GnomAD2 exomes

AF:

0.0743

AC:

18287

AN:

246222

AF XY:

0.0731

show subpopulations

Gnomad AFR exome

AF:

0.00862

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.0325

Gnomad NFE exome

AF:

0.0507

Gnomad OTH exome

AF:

0.0568

GnomAD4 exome

AF:

0.0597

AC:

87107

AN:

1459454

Hom.:

3817

Cov.:

AF XY:

0.0601

AC XY:

43616

AN XY:

725650

show subpopulations

African (AFR)

AF:

0.00861

AC:

288

AN:

33454

American (AMR)

AF:

0.114

AC:

5088

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.0212

AC:

554

AN:

26104

East Asian (EAS)

AF:

0.246

AC:

9765

AN:

39646

South Asian (SAS)

AF:

0.0934

AC:

8052

AN:

86196

European-Finnish (FIN)

AF:

0.0341

AC:

1809

AN:

52998

Middle Eastern (MID)

AF:

0.0389

AC:

221

AN:

5684

European-Non Finnish (NFE)

AF:

0.0519

AC:

57634

AN:

1110478

Other (OTH)

AF:

0.0613

AC:

3696

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5087

10175

15262

20350

25437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2376

4752

7128

9504

11880

<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:

0.0502

AC:

7649

AN:

152220

Hom.:

340

Cov.:

AF XY:

0.0522

AC XY:

3884

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0124

AC:

514

AN:

41548

American (AMR)

AF:

0.0904

AC:

1384

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.234

AC:

1205

AN:

5156

South Asian (SAS)

AF:

0.0992

AC:

478

AN:

4820

European-Finnish (FIN)

AF:

0.0288

AC:

305

AN:

10602

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0518

AC:

3522

AN:

68004

Other (OTH)

AF:

0.0649

AC:

137

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

357

714

1072

1429

1786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0530

Hom.:

918

Bravo

AF:

0.0536

TwinsUK

AF:

0.0539

AC:

200

ALSPAC

AF:

0.0592

AC:

228

ESP6500AA

AF:

0.00965

AC:

ESP6500EA

AF:

0.0494

AC:

412

ExAC

AF:

0.0717

AC:

8677

Asia WGS

AF:

0.182

AC:

631

AN:

3478

EpiCase

AF:

0.0468

EpiControl

AF:

0.0455

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

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

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.83

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

MetaRNN

Benign

0.0039

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L;L;.;.;.

PhyloP100

0.54

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

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

REVEL

Benign

0.12

Sift

Benign

0.17

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

Sift4G

Benign

0.18

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

Polyphen

0.18

B;B;B;B;P;.;B

Vest4

0.068

MPC

0.065

ClinPred

0.0065

GERP RS

3.7

PromoterAI

0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.055

gMVP

0.26

Mutation Taster

=100/0

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

Other links and lift over