chr17-3591067-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_080704.4(TRPV1):c.501C>A(p.His167Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H167R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TRPV1
NM_080704.4 missense

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03066963).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.501C>A	p.His167Gln	missense_variant	Exon 5 of 17	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.501C>A	p.His167Gln	missense_variant	Exon 4 of 16		NP_061197.4	Q8NER1-1
TRPV1	NM_080705.4 link	c.501C>A	p.His167Gln	missense_variant	Exon 4 of 16		NP_542436.2	Q8NER1-1
TRPV1	NM_080706.3 link	c.501C>A	p.His167Gln	missense_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>A	p.His167Gln	missense_variant	Exon 5 of 17	1	NM_080704.4	ENSP00000459962.1	Q8NER1-1
ENSG00000262304	ENST00000572919.1 link	n.*1785C>A		non_coding_transcript_exon_variant	Exon 10 of 14	5		ENSP00000461416.1	A0A0B4J2A0
ENSG00000262304	ENST00000572919.1 link	n.*1785C>A		3_prime_UTR_variant	Exon 10 of 14	5		ENSP00000461416.1	A0A0B4J2A0

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

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

GnomAD2 exomes

AF:

0.0000243

AC:

AN:

246538

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460564

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726434

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

85972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111454

Other (OTH)

AF:

0.00

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000723

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41536

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00377

Hom.:

1046

ExAC

AF:

0.0000495

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.23

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.25

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

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.70

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

M_CAP

Benign

0.023

MetaRNN

Benign

0.031

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

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-0.12

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

PhyloP100

-0.73

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

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

REVEL

Uncertain

0.33

Sift

Benign

0.28

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

Sift4G

Benign

0.54

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

Polyphen

0.0010

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

Vest4

0.16

MutPred

0.37

Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);Loss of catalytic residue at D168 (P = 0.039);

MVP

0.19

MPC

0.065

ClinPred

0.032

GERP RS

-9.0

Varity_R

0.21

gMVP

0.50

Mutation Taster

=84/16

polymorphism

(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