rs2305018

Variant names:

• chr8-72026122-A-C
• rs2305018
• NM_007332.3:c.2938-49T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-72026122-A-C
• chr8-72026122-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007332.3(TRPA1):​c.2938-49T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,411,966 control chromosomes in the GnomAD database, including 43,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4269 hom., cov: 32)
  • Exomes 𝑓: 0.25 (39344 hom.)
• Consequence: TRPA1 NM_007332.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-72026122-A-C is Benign according to our data. Variant chr8-72026122-A-C is described in ClinVar as Benign. ClinVar VariationId is 1342278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 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.2938-49T>G		intron	N/A	NP_015628.2	O75762
	MSC-AS1	NR_033651.1		n.434-26417A>C		intron	N/A
	MSC-AS1	NR_033652.1		n.1029-26417A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.2938-49T>G		intron	N/A	ENSP00000262209.4	O75762
	MSC-AS1	ENST00000457356.9	TSL:1	n.511-26417A>C		intron	N/A
	TRPA1	ENST00000859810.1		c.2938-49T>G		intron	N/A	ENSP00000529869.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34735 AN: 152018 Hom.: 4263 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.250 AC: 60388 AN: 241868 AF XY: 0.243

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.342

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.240

GnomAD4 exome AF: 0.246 AC: 309553 AN: 1259830 Hom.: 39344 Cov.: 17 AF XY: 0.242 AC XY: 153891 AN XY: 636906

African (AFR) AF: 0.154 AC: 4555 AN: 29520

American (AMR) AF: 0.284 AC: 12423 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 5663 AN: 24658

East Asian (EAS) AF: 0.358 AC: 13812 AN: 38618

South Asian (SAS) AF: 0.139 AC: 11332 AN: 81636

European-Finnish (FIN) AF: 0.327 AC: 17097 AN: 52326

Middle Eastern (MID) AF: 0.166 AC: 866 AN: 5216

European-Non Finnish (NFE) AF: 0.249 AC: 231252 AN: 930506

Other (OTH) AF: 0.234 AC: 12553 AN: 53594

GnomAD4 genome AF: 0.229 AC: 34771 AN: 152136 Hom.: 4269 Cov.: 32 AF XY: 0.232 AC XY: 17256 AN XY: 74368

African (AFR) AF: 0.152 AC: 6322 AN: 41498

American (AMR) AF: 0.257 AC: 3927 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3472

East Asian (EAS) AF: 0.345 AC: 1782 AN: 5164

South Asian (SAS) AF: 0.137 AC: 659 AN: 4826

European-Finnish (FIN) AF: 0.335 AC: 3540 AN: 10576

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 17010 AN: 67992

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.244 Hom.: 857

Bravo AF: 0.223

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Familial episodic pain syndrome with predominantly upper body involvement (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.71
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2305018; hg19: chr8-72938357; COSMIC: COSV51555199; COSMIC: COSV51555199;