dbSNP rs3735943: TRPA1:p.Leu544Leu (chr8-72053767-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.73

Publications

27 publications found

Variant links:

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]

TRPA1 links:

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

MSC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPA1	NM_007332.3 link	c.1630C>T	p.Leu544Leu	synonymous_variant	Exon 13 of 27	ENST00000262209.5	NP_015628.2	O75762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5 link	c.1630C>T	p.Leu544Leu	synonymous_variant	Exon 13 of 27	1	NM_007332.3	ENSP00000262209.4		O75762

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78883

AN:

151914

Hom.:

20901

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.508

AC XY:

368715

AN XY:

725228

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

18651

37302

55952

74603

93254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16030

32060

48090

64120

80150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.519

AC:

78966

AN:

152032

Hom.:

20935

Cov.:

AF XY:

0.524

AC XY:

38936

AN XY:

74316

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1912

3824

5735

7647

9559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

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

(source)

DANN

Benign

0.79

PhyloP100

1.7

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over