8-72053767-G-A

Variant names:

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

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
• Publications: 27 publications found

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	NM_007332.3	MANE Select	c.1630C>T	p.Leu544Leu	synonymous	Exon 13 of 27	NP_015628.2
	MSC-AS1	NR_033651.1		n.1662G>A		non_coding_transcript_exon	Exon 3 of 3
	MSC-AS1	NR_033652.1		n.2257G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.1630C>T	p.Leu544Leu	synonymous	Exon 13 of 27	ENSP00000262209.4
	MSC-AS1	ENST00000457356.9	TSL:1	n.1739G>A		non_coding_transcript_exon	Exon 3 of 3
	TRPA1	ENST00000523582.5	TSL:5	c.1186C>T	p.Leu396Leu	synonymous	Exon 10 of 24	ENSP00000428151.1

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

African (AFR) AF: 0.497 AC: 16603 AN: 33376

American (AMR) AF: 0.725 AC: 32304 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 14091 AN: 26104

East Asian (EAS) AF: 0.671 AC: 26619 AN: 39674

South Asian (SAS) AF: 0.555 AC: 47775 AN: 86004

European-Finnish (FIN) AF: 0.520 AC: 27755 AN: 53324

Middle Eastern (MID) AF: 0.501 AC: 2420 AN: 4828

European-Non Finnish (NFE) AF: 0.489 AC: 542478 AN: 1109782

Other (OTH) 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

African (AFR) AF: 0.500 AC: 20722 AN: 41480

American (AMR) AF: 0.637 AC: 9726 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1846 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3572 AN: 5164

South Asian (SAS) AF: 0.570 AC: 2745 AN: 4812

European-Finnish (FIN) AF: 0.504 AC: 5333 AN: 10580

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33309 AN: 67952

Other (OTH) AF: 0.521 AC: 1098 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		1.7
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

Other links and lift over

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