Variant rs35427625 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007332.3(TRPA1):c.1812-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 1,589,380 control chromosomes in the GnomAD database, including 8,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.10 ( 963 hom., cov: 33)

Exomes 𝑓: 0.095 ( 7161 hom. )

Consequence

TRPA1
NM_007332.3 splice_region, intron

Scores

Splicing: ADA: 0.001182

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.87

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:):

MSC-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 8-72050874-G-A is Benign according to our data. Variant chr8-72050874-G-A is described in ClinVar as [Benign]. Clinvar id is 3055480.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPA1	NM_007332.3 linkuse as main transcript	c.1812-3C>T		splice_region_variant, intron_variant		ENST00000262209.5	NP_015628.2	O75762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5 linkuse as main transcript	c.1812-3C>T		splice_region_variant, intron_variant		1	NM_007332.3	ENSP00000262209.4		O75762

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15788

AN:

152026

Hom.:

966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0471

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0993

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.0870

AC:

21560

AN:

247828

Hom.:

1145

AF XY:

0.0898

AC XY:

12060

AN XY:

134254

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.0671

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0444

Gnomad NFE exome

AF:

0.0969

Gnomad OTH exome

AF:

0.0999

GnomAD4 exome

AF:

0.0945

AC:

135857

AN:

1437236

Hom.:

7161

Cov.:

AF XY:

0.0957

AC XY:

68568

AN XY:

716706

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.0707

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0453

Gnomad4 NFE exome

AF:

0.0978

Gnomad4 OTH exome

AF:

0.0947

GnomAD4 genome

AF:

0.104

AC:

15796

AN:

152144

Hom.:

963

Cov.:

AF XY:

0.101

AC XY:

7542

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0471

Gnomad4 NFE

AF:

0.0993

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0978

Hom.:

304

Bravo

AF:

0.107

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRPA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.13

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: -3

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