rs13268757

Variant names:

• chr8-72075403-G-A
• rs13268757
• NM_007332.3:c.7C>T

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRPA1	NM_007332.3	c.7C>T	p.Arg3Cys	missense_variant	Exon 1 of 27	ENST00000262209.5	NP_015628.2
TRPA1	XM_011517624.3	c.82C>T	p.Arg28Cys	missense_variant	Exon 2 of 28		XP_011515926.1
TRPA1	XM_011517625.3	c.7C>T	p.Arg3Cys	missense_variant	Exon 3 of 29		XP_011515927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5	c.7C>T	p.Arg3Cys	missense_variant	Exon 1 of 27	1	NM_007332.3	ENSP00000262209.4

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

GnomAD2 exomes AF: 0.134 AC: 33094 AN: 246796 AF XY: 0.139

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 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

African (AFR) AF: 0.0849 AC: 2834 AN: 33388

American (AMR) AF: 0.0899 AC: 4020 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6954 AN: 26122

East Asian (EAS) AF: 0.0538 AC: 2137 AN: 39692

South Asian (SAS) AF: 0.140 AC: 12068 AN: 86124

European-Finnish (FIN) AF: 0.104 AC: 5164 AN: 49452

Middle Eastern (MID) AF: 0.227 AC: 960 AN: 4234

European-Non Finnish (NFE) AF: 0.156 AC: 172664 AN: 1110188

Other (OTH) AF: 0.153 AC: 9220 AN: 60106

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

African (AFR) AF: 0.0867 AC: 3600 AN: 41530

American (AMR) AF: 0.116 AC: 1769 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3466

East Asian (EAS) AF: 0.0598 AC: 309 AN: 5170

South Asian (SAS) AF: 0.131 AC: 632 AN: 4828

European-Finnish (FIN) AF: 0.0890 AC: 943 AN: 10600

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10863 AN: 67980

Other (OTH) AF: 0.153 AC: 324 AN: 2112

Alfa AF: 0.152 Hom.: 7504

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
PhyloP100		0.15
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
PromoterAI		-0.018	Neutral
Varity_R		0.096
gMVP		0.32
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

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