Genetic Variant TRPA1:c.1644+15C>T (chr8-72053738-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007332.3(TRPA1):c.1644+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,586,502 control chromosomes in the GnomAD database, including 102,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10927 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91851 hom. )

Consequence

TRPA1
NM_007332.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.554

Publications

17 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 8-72053738-G-A is Benign according to our data. Variant chr8-72053738-G-A is described in ClinVar as Benign. ClinVar VariationId is 1342281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPA1	NM_007332.3	MANE Select	c.1644+15C>T	intron	N/A	NP_015628.2	O75762
MSC-AS1	NR_033651.1		n.1633G>A	non_coding_transcript_exon	Exon 3 of 3
MSC-AS1	NR_033652.1		n.2228G>A	non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.1644+15C>T	intron	N/A	ENSP00000262209.4	O75762
MSC-AS1	ENST00000457356.9	TSL:1	n.1710G>A	non_coding_transcript_exon	Exon 3 of 3
TRPA1	ENST00000859810.1		c.1644+15C>T	intron	N/A	ENSP00000529869.1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56278

AN:

151962

Hom.:

10903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.351

GnomAD2 exomes

AF:

0.398

AC:

98558

AN:

247362

AF XY:

0.383

show subpopulations

Gnomad AFR exome

AF:

0.360

Gnomad AMR exome

AF:

0.638

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.411

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.363

GnomAD4 exome

AF:

0.350

AC:

502436

AN:

1434422

Hom.:

91851

Cov.:

AF XY:

0.347

AC XY:

248008

AN XY:

714740

show subpopulations

African (AFR)

AF:

0.366

AC:

12030

AN:

32890

American (AMR)

AF:

0.622

AC:

27529

AN:

44272

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7088

AN:

25948

East Asian (EAS)

AF:

0.546

AC:

21591

AN:

39510

South Asian (SAS)

AF:

0.342

AC:

29128

AN:

85170

European-Finnish (FIN)

AF:

0.415

AC:

22064

AN:

53194

Middle Eastern (MID)

AF:

0.264

AC:

1203

AN:

4550

European-Non Finnish (NFE)

AF:

0.331

AC:

360927

AN:

1089462

Other (OTH)

AF:

0.351

AC:

20876

AN:

59426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

14378

28756

43135

57513

71891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11796

23592

35388

47184

58980

<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:

0.370

AC:

56344

AN:

152080

Hom.:

10927

Cov.:

AF XY:

0.376

AC XY:

27963

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.366

AC:

15193

AN:

41494

American (AMR)

AF:

0.505

AC:

7707

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

947

AN:

3470

East Asian (EAS)

AF:

0.548

AC:

2833

AN:

5170

South Asian (SAS)

AF:

0.355

AC:

1712

AN:

4818

European-Finnish (FIN)

AF:

0.414

AC:

4386

AN:

10582

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.329

AC:

22378

AN:

67972

Other (OTH)

AF:

0.348

AC:

736

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1794

3587

5381

7174

8968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.343

Hom.:

26939

Bravo

AF:

0.382

Asia WGS

AF:

0.465

AC:

1616

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial episodic pain syndrome with predominantly upper body involvement (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.4

(source)

DANN

Benign

0.72

PhyloP100

0.55

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over