dbSNP rs6802503: TRA2B:c.334-118T>G (chr3-185924102-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004593.3(TRA2B):c.334-118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 803,310 control chromosomes in the GnomAD database, including 13,078 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1676 hom., cov: 32)

Exomes 𝑓: 0.18 ( 11402 hom. )

Consequence

TRA2B
NM_004593.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.626

Publications

8 publications found

Variant links:

Genes affected

TRA2B (HGNC:10781): (transformer 2 beta homolog) This gene encodes a nuclear protein which functions as sequence-specific serine/arginine splicing factor which plays a role in mRNA processing, splicing patterns, and gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

TRA2B Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P
complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

TRA2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004593.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRA2B	NM_004593.3	MANE Select	c.334-118T>G		intron	N/A	NP_004584.1	P62995-1
	TRA2B	NM_001243879.2		c.34-118T>G		intron	N/A	NP_001230808.1	P62995-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRA2B	ENST00000453386.7	TSL:1 MANE Select	c.334-118T>G	intron	N/A	ENSP00000416959.2	P62995-1
TRA2B	ENST00000487615.5	TSL:1	n.3566-118T>G	intron	N/A
TRA2B	ENST00000492417.5	TSL:1	n.2637-118T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19349

AN:

152160

Hom.:

1675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0853

Gnomad EAS

AF:

0.0535

Gnomad SAS

AF:

0.0484

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.179

AC:

116345

AN:

651032

Hom.:

11402

Cov.:

AF XY:

0.177

AC XY:

58020

AN XY:

328606

show subpopulations

African (AFR)

AF:

0.0313

AC:

474

AN:

15132

American (AMR)

AF:

0.114

AC:

1606

AN:

14034

Ashkenazi Jewish (ASJ)

AF:

0.0955

AC:

1323

AN:

13858

East Asian (EAS)

AF:

0.0600

AC:

1777

AN:

29634

South Asian (SAS)

AF:

0.0661

AC:

2218

AN:

33560

European-Finnish (FIN)

AF:

0.143

AC:

4215

AN:

29490

Middle Eastern (MID)

AF:

0.0602

AC:

225

AN:

3736

European-Non Finnish (NFE)

AF:

0.208

AC:

99644

AN:

479938

Other (OTH)

AF:

0.154

AC:

4863

AN:

31650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4575

9150

13725

18300

22875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2492

4984

7476

9968

12460

<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:

0.127

AC:

19344

AN:

152278

Hom.:

1676

Cov.:

AF XY:

0.121

AC XY:

9042

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0334

AC:

1390

AN:

41570

American (AMR)

AF:

0.113

AC:

1723

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0853

AC:

296

AN:

3470

East Asian (EAS)

AF:

0.0534

AC:

277

AN:

5188

South Asian (SAS)

AF:

0.0483

AC:

233

AN:

4826

European-Finnish (FIN)

AF:

0.133

AC:

1408

AN:

10602

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13598

AN:

68006

Other (OTH)

AF:

0.134

AC:

283

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

827

1653

2480

3306

4133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<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:

0.172

Hom.:

5496

Bravo

AF:

0.126

Asia WGS

AF:

0.0450

AC:

156

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.2

(source)

DANN

Benign

0.38

PhyloP100

0.63

PromoterAI

0.010

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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