dbSNP rs3824151: TRPA1:c.2869-6C>A (chr8-72029975-G-T) – 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.2869-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,610,630 control chromosomes in the GnomAD database, including 299,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30320 hom., cov: 32)

Exomes 𝑓: 0.61 ( 269409 hom. )

Consequence

TRPA1
NM_007332.3 splice_region, intron

Scores

Splicing: ADA: 0.001980

Clinical Significance

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

Conservation

PhyloP100: -0.483

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-72029975-G-T is Benign according to our data. Variant chr8-72029975-G-T is described in ClinVar as Benign. ClinVar VariationId is 1342279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 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.2869-6C>A	splice_region intron	N/A	NP_015628.2	O75762
MSC-AS1	NR_033651.1		n.434-22564G>T	intron	N/A
MSC-AS1	NR_033652.1		n.1029-22564G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.2869-6C>A	splice_region intron	N/A	ENSP00000262209.4	O75762
MSC-AS1	ENST00000457356.9	TSL:1	n.511-22564G>T	intron	N/A
TRPA1	ENST00000859810.1		c.2869-6C>A	splice_region intron	N/A	ENSP00000529869.1

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95450

AN:

151900

Hom.:

30277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.656

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.741

Gnomad ASJ

AF:

0.649

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.672

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.682

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.638

GnomAD2 exomes

AF:

0.643

AC:

161375

AN:

250870

AF XY:

0.637

show subpopulations

Gnomad AFR exome

AF:

0.651

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.686

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.594

Gnomad OTH exome

AF:

0.634

GnomAD4 exome

AF:

0.605

AC:

882891

AN:

1458610

Hom.:

269409

Cov.:

AF XY:

0.606

AC XY:

439736

AN XY:

725742

show subpopulations

African (AFR)

AF:

0.659

AC:

22021

AN:

33410

American (AMR)

AF:

0.798

AC:

35642

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

17111

AN:

26102

East Asian (EAS)

AF:

0.671

AC:

26606

AN:

39660

South Asian (SAS)

AF:

0.667

AC:

57514

AN:

86180

European-Finnish (FIN)

AF:

0.567

AC:

30274

AN:

53416

Middle Eastern (MID)

AF:

0.656

AC:

3777

AN:

5762

European-Non Finnish (NFE)

AF:

0.588

AC:

652565

AN:

1109104

Other (OTH)

AF:

0.620

AC:

37381

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

17267

34534

51800

69067

86334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17998

35996

53994

71992

89990

<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:

0.628

AC:

95541

AN:

152020

Hom.:

30320

Cov.:

AF XY:

0.631

AC XY:

46870

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.656

AC:

27218

AN:

41464

American (AMR)

AF:

0.741

AC:

11329

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.649

AC:

2253

AN:

3470

East Asian (EAS)

AF:

0.693

AC:

3590

AN:

5178

South Asian (SAS)

AF:

0.672

AC:

3235

AN:

4814

European-Finnish (FIN)

AF:

0.552

AC:

5817

AN:

10532

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40069

AN:

67962

Other (OTH)

AF:

0.636

AC:

1343

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1784

3568

5353

7137

8921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.585

Hom.:

7290

Bravo

AF:

0.643

Asia WGS

AF:

0.696

AC:

2422

AN:

3476

EpiCase

AF:

0.588

EpiControl

AF:

0.587

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

-0.80

CADD

Benign

0.23

(source)

DANN

Benign

0.68

PhyloP100

-0.48

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0020

dbscSNV1_RF

Benign

0.26

Splicevardb

2.0

SpliceAI score (max)

0.050

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