Genetic Variant TAB2:c.6+26913A>G (chr6-149245689-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001292035.3(TAB2):c.6+26913A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,752 control chromosomes in the GnomAD database, including 22,073 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 0.54 ( 22072 hom., cov: 30)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

TAB2
NM_001292035.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375

Publications

2 publications found

Variant links:

COSMIC-nc: COSV70064232

Genes affected

TAB2 (HGNC:17075): (TGF-beta activated kinase 1 (MAP3K7) binding protein 2) The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, and it thus serves as an adaptor that links MAP3K7 and TRAF6. This protein, along with TAB1 and MAP3K7, also participates in the signal transduction induced by TNFSF11/RANKl through the activation of the receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Studies of the related mouse protein indicate that it functions to protect against liver damage caused by chemical stressors. Mutations in this gene cause congenital heart defects, multiple types, 2 (CHTD2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

TAB2 links:

TAB2-AS1 (HGNC:53508): (TAB2 antisense RNA 1)

TAB2-AS1 links:

ENSG00000228408 (HGNC:):

ENSG00000228408 links:

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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=-0.96).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292035.3 link	c.6+26913A>G		intron_variant	Intron 2 of 6		NP_001278964.1
TAB2-AS1	NR_149096.1 link	n.169-1688T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
TAB2	ENST00000606202.1 link	c.-121+26913A>G	intron_variant	Intron 1 of 1	4	ENSP00000476139.1
TAB2-AS1	ENST00000424421.3 link	n.175-1688T>C	intron_variant	Intron 1 of 2	5
ENSG00000228408	ENST00000635954.1 link	n.*135A>G	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81361

AN:

151630

Hom.:

22040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.537

AC:

81448

AN:

151748

Hom.:

22072

Cov.:

AF XY:

0.537

AC XY:

39798

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.517

AC:

21349

AN:

41330

American (AMR)

AF:

0.662

AC:

10097

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1507

AN:

3464

East Asian (EAS)

AF:

0.569

AC:

2914

AN:

5124

South Asian (SAS)

AF:

0.481

AC:

2309

AN:

4802

European-Finnish (FIN)

AF:

0.531

AC:

5593

AN:

10526

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.529

AC:

35924

AN:

67938

Other (OTH)

AF:

0.538

AC:

1132

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1904

3807

5711

7614

9518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.536

Hom.:

64039

Bravo

AF:

0.551

Asia WGS

AF:

0.500

AC:

1743

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.2

(source)

DANN

Benign

0.51

PhyloP100

-0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over