rs13268757

Positions:

• chr8-72075403-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007332.3(TRPA1):​c.7C>T​(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,606,200 control chromosomes in the GnomAD database, including 18,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1439 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17065 hom.)
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014849901).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPA1	NM_007332.3	c.7C>T	p.Arg3Cys	missense_variant	1/27	ENST00000262209.5	NP_015628.2
TRPA1	XM_011517624.3	c.82C>T	p.Arg28Cys	missense_variant	2/28		XP_011515926.1
TRPA1	XM_011517625.3	c.7C>T	p.Arg3Cys	missense_variant	3/29		XP_011515927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5	c.7C>T	p.Arg3Cys	missense_variant	1/27	1	NM_007332.3	ENSP00000262209.4
MSC-AS1	ENST00000518916.5	n.470-1118G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19493 AN: 152068 Hom.: 1439 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.134 AC: 33094 AN: 246796 Hom.: 2567 AF XY: 0.139 AC XY: 18625 AN XY: 133690

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.0855

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.0551

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.149 AC: 216021 AN: 1454014 Hom.: 17065 Cov.: 31 AF XY: 0.150 AC XY: 108593 AN XY: 723528

Gnomad4 AFR exome AF: 0.0849

Gnomad4 AMR exome AF: 0.0899

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.0538

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.128 AC: 19503 AN: 152186 Hom.: 1439 Cov.: 32 AF XY: 0.126 AC XY: 9376 AN XY: 74410

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.0598

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0890

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.153

Alfa AF: 0.161 Hom.: 3498

Bravo AF: 0.128

TwinsUK AF: 0.165 AC: 612

ALSPAC AF: 0.152 AC: 584

ESP6500AA AF: 0.0828 AC: 365

ESP6500EA AF: 0.167 AC: 1437

ExAC AF: 0.135 AC: 16369

Asia WGS AF: 0.0870 AC: 305 AN: 3478

EpiCase AF: 0.171

EpiControl AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.049
Sift	Benign	0.042	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.012	B
Vest4		0.068
MPC		0.089
ClinPred		0.022	T
GERP RS		2.7
Varity_R		0.096
gMVP		0.32

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: rs13268757; hg19: chr8-72987638; COSMIC: COSV51555448;