8-72026122-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 1.02

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

Verdict is Benign. Variant got -14 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 id is 1342278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.2938-49T>G		intron_variant		ENST00000262209.5
MSC-AS1	NR_033652.1	n.1029-26417A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.2938-49T>G		intron_variant		1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.392-26417A>C		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.250 AC: 60388 AN: 241868 Hom.: 8022 AF XY: 0.243 AC XY: 31820 AN XY: 130810

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 SAS exome AF: 0.137

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

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.234

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

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.207

Alfa AF: 0.244 Hom.: 857

Bravo AF: 0.223

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial episodic pain syndrome with predominantly upper body involvement Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.0
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2305018; hg19: chr8-72938357; COSMIC: COSV51555199; COSMIC: COSV51555199;