Genetic Variant 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):

complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRA2B	NM_004593.3 link	c.334-118T>G	intron_variant	Intron 3 of 8	ENST00000453386.7	NP_004584.1	P62995-1
TRA2B	NM_001243879.2 link	c.34-118T>G	intron_variant	Intron 2 of 7		NP_001230808.1	P62995-3
TRA2B	XM_047448717.1 link	c.34-118T>G	intron_variant	Intron 3 of 8		XP_047304673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRA2B	ENST00000453386.7 link	c.334-118T>G		intron_variant	Intron 3 of 8	1	NM_004593.3	ENSP00000416959.2		P62995-1

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over