rs920829

Variant names:

• chr8-72065468-C-T
• rs920829
• NM_007332.3:c.535G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (2459 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12617 hom.)
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.80
• Publications: 47 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 -13 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 VariationId is 3060717.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	NM_007332.3	MANE Select	c.535G>A	p.Glu179Lys	missense	Exon 4 of 27	NP_015628.2	O75762

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.535G>A	p.Glu179Lys	missense	Exon 4 of 27	ENSP00000262209.4	O75762
	TRPA1	ENST00000859810.1		c.535G>A	p.Glu179Lys	missense	Exon 6 of 29	ENSP00000529869.1
	TRPA1	ENST00000523582.5	TSL:5	c.91G>A	p.Glu31Lys	missense	Exon 1 of 24	ENSP00000428151.1	H0YAW0

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

GnomAD2 exomes AF: 0.138 AC: 34731 AN: 251026 AF XY: 0.139

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 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

African (AFR) AF: 0.278 AC: 9286 AN: 33418

American (AMR) AF: 0.0706 AC: 3154 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3543 AN: 26102

East Asian (EAS) AF: 0.311 AC: 12309 AN: 39578

South Asian (SAS) AF: 0.181 AC: 15606 AN: 86200

European-Finnish (FIN) AF: 0.114 AC: 6081 AN: 53360

Middle Eastern (MID) AF: 0.129 AC: 742 AN: 5748

European-Non Finnish (NFE) AF: 0.108 AC: 120367 AN: 1110990

Other (OTH) AF: 0.130 AC: 7812 AN: 60290

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

African (AFR) AF: 0.276 AC: 11438 AN: 41482

American (AMR) AF: 0.0891 AC: 1363 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1476 AN: 5166

South Asian (SAS) AF: 0.180 AC: 869 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1165 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7345 AN: 67982

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.128 Hom.: 5978

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TRPA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.8
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.34
Sift	Benign	0.12	T
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.23
MPC		0.38
ClinPred		0.025	T
GERP RS		5.4
PromoterAI		-0.0075	Neutral
Varity_R		0.47
gMVP		0.55
Mutation Taster		=87/13	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: rs920829; hg19: chr8-72977703; COSMIC: COSV51556925; COSMIC: COSV51556925;