8-72036353-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_007332.3(TRPA1):c.2490G>A(p.Leu830=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 1,613,898 control chromosomes in the GnomAD database, including 7,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (526 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6932 hom.)
• Consequence: TRPA1 NM_007332.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.444

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-72036353-C-T is Benign according to our data. Variant chr8-72036353-C-T is described in ClinVar as [Benign]. Clinvar id is 3056632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.444 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.2490G>A	p.Leu830=	synonymous_variant	21/27	ENST00000262209.5
MSC-AS1	NR_033652.1	n.1029-16186C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.2490G>A	p.Leu830=	synonymous_variant	21/27	1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.392-16186C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10431 AN: 152168 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.0876

GnomAD3 exomes AF: 0.0773 AC: 19404 AN: 251124 Hom.: 956 AF XY: 0.0826 AC XY: 11215 AN XY: 135738

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.0598

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.0441

Gnomad NFE exome AF: 0.0964

Gnomad OTH exome AF: 0.0944

GnomAD4 exome AF: 0.0920 AC: 134503 AN: 1461612 Hom.: 6932 Cov.: 32 AF XY: 0.0935 AC XY: 67993 AN XY: 727112

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.0624

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.0454

Gnomad4 NFE exome AF: 0.0990

Gnomad4 OTH exome AF: 0.0879

GnomAD4 genome AF: 0.0685 AC: 10430 AN: 152286 Hom.: 526 Cov.: 32 AF XY: 0.0673 AC XY: 5008 AN XY: 74464

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.0862

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0471

Gnomad4 NFE AF: 0.0989

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0964 Hom.: 1270

Bravo AF: 0.0663

Asia WGS AF: 0.0510 AC: 176 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.105

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TRPA1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	6.3
Dann	Benign	0.84

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: rs13280644; hg19: chr8-72948588;