rs3735943

Positions:

• chr8-72053767-G-A
• chr8-72053767-G-C

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.1630C>T​(p.Leu544=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,609,828 control chromosomes in the GnomAD database, including 212,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20935 hom., cov: 32)
  • Exomes 𝑓: 0.51 (191217 hom.)
• Consequence: TRPA1 NM_007332.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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=-0.79).
• BP6: Variant 8-72053767-G-A is Benign according to our data. Variant chr8-72053767-G-A is described in ClinVar as [Benign]. Clinvar id is 1342282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.1630C>T	p.Leu544=	synonymous_variant	13/27	ENST00000262209.5
MSC-AS1	NR_033652.1	n.2257G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.1630C>T	p.Leu544=	synonymous_variant	13/27	1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.469+1151G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78883 AN: 151914 Hom.: 20901 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.522

GnomAD3 exomes AF: 0.554 AC: 138305 AN: 249818 Hom.: 39427 AF XY: 0.545 AC XY: 73531 AN XY: 134960

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.736

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.684

Gnomad SAS exome AF: 0.556

Gnomad FIN exome AF: 0.514

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.531

GnomAD4 exome AF: 0.509 AC: 741460 AN: 1457796 Hom.: 191217 Cov.: 34 AF XY: 0.508 AC XY: 368715 AN XY: 725228

Gnomad4 AFR exome AF: 0.497

Gnomad4 AMR exome AF: 0.725

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.671

Gnomad4 SAS exome AF: 0.555

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.519 AC: 78966 AN: 152032 Hom.: 20935 Cov.: 32 AF XY: 0.524 AC XY: 38936 AN XY: 74316

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.521

Alfa AF: 0.504 Hom.: 32400

Bravo AF: 0.531

Asia WGS AF: 0.640 AC: 2227 AN: 3478

EpiCase AF: 0.486

EpiControl AF: 0.479

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.79

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: rs3735943; hg19: chr8-72966002; COSMIC: COSV100083307; COSMIC: COSV100083307;