rs61758121

Variant names:

• chr8-72026025-G-A
• rs61758121
• NM_007332.3:c.2986C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-72026025-G-A
• chr8-72026025-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_007332.3(TRPA1):​c.2986C>T​(p.Arg996Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,614,014 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.48
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012704015).
• BP6: Variant 8-72026025-G-A is Benign according to our data. Variant chr8-72026025-G-A is described in ClinVar as Benign. ClinVar VariationId is 1711678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 154 AD,Unknown gene.

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.2986C>T	p.Arg996Cys	missense	Exon 25 of 27	NP_015628.2	O75762
	MSC-AS1	NR_033651.1		n.434-26514G>A		intron	N/A
	MSC-AS1	NR_033652.1		n.1029-26514G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.2986C>T	p.Arg996Cys	missense	Exon 25 of 27	ENSP00000262209.4	O75762
	MSC-AS1	ENST00000457356.9	TSL:1	n.511-26514G>A		intron	N/A
	TRPA1	ENST00000859810.1		c.2986C>T	p.Arg996Cys	missense	Exon 27 of 29	ENSP00000529869.1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 154 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000251 AC: 63 AN: 251308 AF XY: 0.000169

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000104 AC: 152 AN: 1461672 Hom.: 1 Cov.: 31 AF XY: 0.000111 AC XY: 81 AN XY: 727150

African (AFR) AF: 0.00272 AC: 91 AN: 33462

American (AMR) AF: 0.000157 AC: 7 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111882

Other (OTH) AF: 0.000199 AC: 12 AN: 60380

GnomAD4 genome AF: 0.00101 AC: 154 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000926 AC XY: 69 AN XY: 74496

African (AFR) AF: 0.00349 AC: 145 AN: 41570

American (AMR) AF: 0.000327 AC: 5 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000518 Hom.: 0

Bravo AF: 0.00107

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000379 AC: 46

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	TRPA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.5
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.15
Sift	Benign	0.045	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.38
MVP		0.74
MPC		0.38
ClinPred		0.081	T
GERP RS		2.7
Varity_R		0.17
gMVP		0.71
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs61758121; hg19: chr8-72938260; COSMIC: COSV51575744; COSMIC: COSV51575744;