17-3573900-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_080704.4(TRPV1):c.1836G>A(p.Thr612=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,610,324 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 28 hom., cov: 30)

Exomes 𝑓: 0.0014 ( 30 hom. )

Consequence

TRPV1
NM_080704.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-3573900-C-T is Benign according to our data. Variant chr17-3573900-C-T is described in ClinVar as [Benign]. Clinvar id is 778654.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1743/151932) while in subpopulation AFR AF= 0.0396 (1641/41420). AF 95% confidence interval is 0.038. There are 28 homozygotes in gnomad4. There are 816 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd at 1732 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRPV1	NM_080704.4 linkuse as main transcript	c.1836G>A	p.Thr612=	synonymous_variant	14/17	ENST00000572705.2
TRPV1	NM_018727.5 linkuse as main transcript	c.1836G>A	p.Thr612=	synonymous_variant	13/16
TRPV1	NM_080705.4 linkuse as main transcript	c.1836G>A	p.Thr612=	synonymous_variant	13/16
TRPV1	NM_080706.3 linkuse as main transcript	c.1836G>A	p.Thr612=	synonymous_variant	12/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2 linkuse as main transcript	c.1836G>A	p.Thr612=	synonymous_variant	14/17	1	NM_080704.4	P1	Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1732

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00375

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00315

AC:

770

AN:

244388

Hom.:

AF XY:

0.00251

AC XY:

334

AN XY:

133046

show subpopulations

Gnomad AFR exome

AF:

0.0415

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000226

Gnomad OTH exome

AF:

0.00169

GnomAD4 exome

AF:

0.00142

AC:

2075

AN:

1458392

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

994

AN XY:

725600

show subpopulations

Gnomad4 AFR exome

AF:

0.0451

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00164

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00309

GnomAD4 genome

AF:

0.0115

AC:

1743

AN:

151932

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

816

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0396

Gnomad4 AMR

AF:

0.00374

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00713

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

0.54

Dann

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over