rs3735943

Variant names:

• chr8-72053767-G-A
• rs3735943
• NM_007332.3:c.1630C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007332.3(TRPA1):​c.1630C>T​(p.Leu544Leu) 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -21 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TRPA1	NM_007332.3	c.1630C>T	p.Leu544Leu	synonymous_variant	Exon 13 of 27	ENST00000262209.5	NP_015628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5	c.1630C>T	p.Leu544Leu	synonymous_variant	Exon 13 of 27	1	NM_007332.3	ENSP00000262209.4

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

GnomAD2 exomes AF: 0.554 AC: 138305 AN: 249818 AF XY: 0.545

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 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 AC: 16603 AN: 33376

Gnomad4 AMR exome AF: 0.725 AC: 32304 AN: 44560

Gnomad4 ASJ exome AF: 0.540 AC: 14091 AN: 26104

Gnomad4 EAS exome AF: 0.671 AC: 26619 AN: 39674

Gnomad4 SAS exome AF: 0.555 AC: 47775 AN: 86004

Gnomad4 FIN exome AF: 0.520 AC: 27755 AN: 53324

Gnomad4 NFE exome AF: 0.489 AC: 542478 AN: 1109782

Gnomad4 Remaining exome AF: 0.522 AC: 31415 AN: 60144

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 AC: 0.499566 AN: 0.499566

Gnomad4 AMR AF: 0.637 AC: 0.637436 AN: 0.637436

Gnomad4 ASJ AF: 0.532 AC: 0.531682 AN: 0.531682

Gnomad4 EAS AF: 0.692 AC: 0.691712 AN: 0.691712

Gnomad4 SAS AF: 0.570 AC: 0.570449 AN: 0.570449

Gnomad4 FIN AF: 0.504 AC: 0.504064 AN: 0.504064

Gnomad4 NFE AF: 0.490 AC: 0.490184 AN: 0.490184

Gnomad4 OTH AF: 0.521 AC: 0.520873 AN: 0.520873

Alfa AF: 0.506 Hom.: 39697

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.79
Mutation Taster		=97/3	polymorphism (auto)

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;