8-72026097-G-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.2938-24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,575,902 control chromosomes in the GnomAD database, including 54,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4181 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50794 hom.)
• Consequence: TRPA1 NM_007332.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.01

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=-0.84).
• BP6: Variant 8-72026097-G-C is Benign according to our data. Variant chr8-72026097-G-C is described in ClinVar as [Benign]. Clinvar id is 1342277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.2938-24C>G		intron_variant		ENST00000262209.5
MSC-AS1	NR_033652.1	n.1029-26442G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.2938-24C>G		intron_variant		1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.392-26442G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34143 AN: 152108 Hom.: 4180 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.252 AC: 62748 AN: 249216 Hom.: 8533 AF XY: 0.262 AC XY: 35327 AN XY: 134640

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.358

Gnomad SAS exome AF: 0.315

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.262 AC: 373350 AN: 1423676 Hom.: 50794 Cov.: 23 AF XY: 0.266 AC XY: 188966 AN XY: 710592

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.224 AC: 34165 AN: 152226 Hom.: 4181 Cov.: 32 AF XY: 0.225 AC XY: 16753 AN XY: 74436

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.255

Alfa AF: 0.202 Hom.: 704

Bravo AF: 0.217

Asia WGS AF: 0.266 AC: 924 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	-0.84
Cadd	Benign	7.1
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2305017; hg19: chr8-72938332; COSMIC: COSV51569972; COSMIC: COSV51569972;