8-72050874-G-A

Variant names:

• chr8-72050874-G-A
• rs35427625
• NM_007332.3:c.1812-3C>T

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.1812-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 1,589,380 control chromosomes in the GnomAD database, including 8,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (963 hom., cov: 33)
  • Exomes 𝑓: 0.095 (7161 hom.)
• Consequence: TRPA1 NM_007332.3 splice_region, intron
• Scores: Splicing: ADA: 0.001182
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.87
• Publications: 6 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 (BayesDel_noAF=-0.49).
• BP6: Variant 8-72050874-G-A is Benign according to our data. Variant chr8-72050874-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055480.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	NM_007332.3	MANE Select	c.1812-3C>T		splice_region intron	N/A	NP_015628.2
	MSC-AS1	NR_033651.1		n.434-1665G>A		intron	N/A
	MSC-AS1	NR_033652.1		n.1029-1665G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.1812-3C>T		splice_region intron	N/A	ENSP00000262209.4
	MSC-AS1	ENST00000457356.9	TSL:1	n.511-1665G>A		intron	N/A
	TRPA1	ENST00000523582.5	TSL:5	c.1368-3C>T		splice_region intron	N/A	ENSP00000428151.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15788 AN: 152026 Hom.: 966 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.0870 AC: 21560 AN: 247828 AF XY: 0.0898

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0671

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.000436

Gnomad FIN exome AF: 0.0444

Gnomad NFE exome AF: 0.0969

Gnomad OTH exome AF: 0.0999

GnomAD4 exome AF: 0.0945 AC: 135857 AN: 1437236 Hom.: 7161 Cov.: 27 AF XY: 0.0957 AC XY: 68568 AN XY: 716706

African (AFR) AF: 0.140 AC: 4621 AN: 32904

American (AMR) AF: 0.0707 AC: 3149 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2984 AN: 25928

East Asian (EAS) AF: 0.000354 AC: 14 AN: 39510

South Asian (SAS) AF: 0.112 AC: 9618 AN: 85740

European-Finnish (FIN) AF: 0.0453 AC: 2319 AN: 51204

Middle Eastern (MID) AF: 0.131 AC: 747 AN: 5682

European-Non Finnish (NFE) AF: 0.0978 AC: 106762 AN: 1092116

Other (OTH) AF: 0.0947 AC: 5643 AN: 59584

GnomAD4 genome AF: 0.104 AC: 15796 AN: 152144 Hom.: 963 Cov.: 33 AF XY: 0.101 AC XY: 7542 AN XY: 74384

African (AFR) AF: 0.139 AC: 5780 AN: 41492

American (AMR) AF: 0.100 AC: 1532 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.103 AC: 495 AN: 4818

European-Finnish (FIN) AF: 0.0471 AC: 500 AN: 10612

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0993 AC: 6752 AN: 67988

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.101 Hom.: 458

Bravo AF: 0.107

Asia WGS AF: 0.0560 AC: 195 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TRPA1-related disorder Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		1.9
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.13
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35427625; hg19: chr8-72963109;