rs920829

chr8-72065468-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007332.3(TRPA1):c.535G>A(p.Glu179Lys) variant causes a missense change. The variant allele was found at a frequency of 0.126 in 1,612,456 control chromosomes in the GnomAD database, including 15,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2459 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12617 hom.)
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.80

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]

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017194152).
• BP6: Variant 8-72065468-C-T is Benign according to our data. Variant chr8-72065468-C-T is described in ClinVar as [Benign]. Clinvar id is 3060717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.535G>A	p.Glu179Lys	missense_variant	4/27	ENST00000262209.5
TRPA1	XM_011517624.3	c.610G>A	p.Glu204Lys	missense_variant	5/28
TRPA1	XM_011517625.3	c.535G>A	p.Glu179Lys	missense_variant	6/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.535G>A	p.Glu179Lys	missense_variant	4/27	1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.470-11053C>T		intron_variant, non_coding_transcript_variant		3
TRPA1	ENST00000523582.5	c.91G>A	p.Glu31Lys	missense_variant	1/24	5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24564 AN: 151996 Hom.: 2453 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.138 AC: 34731 AN: 251026 Hom.: 3055 AF XY: 0.139 AC XY: 18864 AN XY: 135666

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.0693

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.305

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.123 AC: 178900 AN: 1460342 Hom.: 12617 Cov.: 31 AF XY: 0.124 AC XY: 89978 AN XY: 726514

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.0706

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.162 AC: 24583 AN: 152114 Hom.: 2459 Cov.: 32 AF XY: 0.161 AC XY: 11950 AN XY: 74348

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.157

Alfa AF: 0.123 Hom.: 2840

Bravo AF: 0.163

TwinsUK AF: 0.101 AC: 374

ALSPAC AF: 0.0963 AC: 371

ESP6500AA AF: 0.278 AC: 1223

ESP6500EA AF: 0.109 AC: 937

ExAC AF: 0.143 AC: 17381

Asia WGS AF: 0.193 AC: 670 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.108

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TRPA1-related disorder Benign:1

Benign, criteria provided, single submitter

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Uncertain	0.020
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.2	T
MutationTaster	Benign	7.0e-8	P
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Uncertain	0.34
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.043	D;D
Polyphen		0.99	.;D
Vest4		0.23
MPC		0.38
ClinPred		0.025	T
GERP RS		5.4
Varity_R		0.47
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs920829; hg19: chr8-72977703; COSMIC: COSV51556925; COSMIC: COSV51556925;