Genetic Variant TRPV1:p.His167His (chr17-3591067-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_080704.4(TRPV1):c.501C>T(p.His167His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,612,620 control chromosomes in the GnomAD database, including 13,651 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1000 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12651 hom. )

Consequence

TRPV1
NM_080704.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.727

Publications

24 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-0.727 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.501C>T	p.His167His	synonymous_variant	Exon 5 of 17	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.501C>T	p.His167His	synonymous_variant	Exon 4 of 16		NP_061197.4	Q8NER1-1
TRPV1	NM_080705.4 link	c.501C>T	p.His167His	synonymous_variant	Exon 4 of 16		NP_542436.2	Q8NER1-1
TRPV1	NM_080706.3 link	c.501C>T	p.His167His	synonymous_variant	Exon 3 of 15		NP_542437.2	Q8NER1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPV1	ENST00000572705.2 link	c.501C>T	p.His167His	synonymous_variant	Exon 5 of 17	1	NM_080704.4	ENSP00000459962.1	Q8NER1-1
ENSG00000262304	ENST00000572919.1 link	n.*1785C>T		non_coding_transcript_exon_variant	Exon 10 of 14	5		ENSP00000461416.1	A0A0B4J2A0
ENSG00000262304	ENST00000572919.1 link	n.*1785C>T		3_prime_UTR_variant	Exon 10 of 14	5		ENSP00000461416.1	A0A0B4J2A0

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15792

AN:

152088

Hom.:

998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.136

AC:

33621

AN:

246538

AF XY:

0.139

show subpopulations

Gnomad AFR exome

AF:

0.0365

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.125

AC:

181881

AN:

1460414

Hom.:

12651

Cov.:

AF XY:

0.127

AC XY:

92205

AN XY:

726360

show subpopulations

African (AFR)

AF:

0.0368

AC:

1233

AN:

33468

American (AMR)

AF:

0.141

AC:

6264

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

3186

AN:

26096

East Asian (EAS)

AF:

0.265

AC:

10512

AN:

39654

South Asian (SAS)

AF:

0.222

AC:

19119

AN:

85952

European-Finnish (FIN)

AF:

0.123

AC:

6565

AN:

53346

Middle Eastern (MID)

AF:

0.136

AC:

781

AN:

5740

European-Non Finnish (NFE)

AF:

0.114

AC:

126561

AN:

1111386

Other (OTH)

AF:

0.127

AC:

7660

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

10489

20977

31466

41954

52443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4842

9684

14526

19368

24210

<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:

0.104

AC:

15802

AN:

152206

Hom.:

1000

Cov.:

AF XY:

0.107

AC XY:

7993

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0415

AC:

1723

AN:

41534

American (AMR)

AF:

0.126

AC:

1931

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

430

AN:

3470

East Asian (EAS)

AF:

0.250

AC:

1290

AN:

5166

South Asian (SAS)

AF:

0.238

AC:

1148

AN:

4824

European-Finnish (FIN)

AF:

0.121

AC:

1280

AN:

10608

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7690

AN:

67994

Other (OTH)

AF:

0.109

AC:

231

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

721

1442

2162

2883

3604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0997

Hom.:

1046

Bravo

AF:

0.0984

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.53

PhyloP100

-0.73

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