8-72023910-T-C

Position:

chr8-72023910-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007332.3(TRPA1):c.3053A>G(p.His1018Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,557,990 control chromosomes in the GnomAD database, including 24,907 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1921 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22986 hom. )

Consequence

TRPA1
NM_007332.3 missense, splice_region

Scores

Splicing: ADA: 0.00001829

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.421

Variant links:

Genes affected

TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]

TRPA1 links:

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

MSC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057715178).

BP6

Variant 8-72023910-T-C is Benign according to our data. Variant chr8-72023910-T-C is described in ClinVar as [Benign]. Clinvar id is 1342276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPA1	NM_007332.3 link	c.3053A>G	p.His1018Arg	missense_variant, splice_region_variant	26/27	ENST00000262209.5	NP_015628.2	O75762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5 link	c.3053A>G	p.His1018Arg	missense_variant, splice_region_variant	26/27	1	NM_007332.3	ENSP00000262209.4		O75762

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21186

AN:

152130

Hom.:

1922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0433

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.161

GnomAD3 exomes

AF:

0.179

AC:

44592

AN:

249376

Hom.:

4895

AF XY:

0.188

AC XY:

25409

AN XY:

134842

show subpopulations

Gnomad AFR exome

AF:

0.0406

Gnomad AMR exome

AF:

0.0854

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.172

AC:

241151

AN:

1405742

Hom.:

22986

Cov.:

AF XY:

0.176

AC XY:

123703

AN XY:

702296

show subpopulations

Gnomad4 AFR exome

AF:

0.0384

Gnomad4 AMR exome

AF:

0.0874

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.378

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.139

AC:

21187

AN:

152248

Hom.:

1921

Cov.:

AF XY:

0.141

AC XY:

10478

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0434

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.242

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.177

Hom.:

6235

Bravo

AF:

0.131

TwinsUK

AF:

0.165

AC:

610

ALSPAC

AF:

0.160

AC:

616

ESP6500AA

AF:

0.0508

AC:

223

ESP6500EA

AF:

0.178

AC:

1524

ExAC

AF:

0.180

AC:

21880

Asia WGS

AF:

0.240

AC:

833

AN:

3476

EpiCase

AF:

0.175

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

TRPA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Familial episodic pain syndrome with predominantly upper body involvement

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.54

DANN

Benign

0.41

DEOGEN2

Benign

0.075

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00099

LIST_S2

Benign

0.22

T;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.7

.;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.031

Sift

Benign

0.56

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0

.;B

Vest4

0.012

MPC

0.12

ClinPred

0.0062

GERP RS

0.88

Varity_R

0.036

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0060

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

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