rs9373589

Variant names:

• chr6-149386152-A-G
• rs9373589
• NM_001292034.3:c.1603+6634A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-149386152-A-G
• chr6-149386152-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292034.3(TAB2):​c.1603+6634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,020 control chromosomes in the GnomAD database, including 10,120 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 0.36 (10120 hom., cov: 32)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• chromosome 6q24-q25 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• congenital heart defects, multiple types, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• polyvalvular heart disease syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292034.3	c.1603+6634A>G		intron_variant	Intron 3 of 6	ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2	c.1603+6634A>G		intron_variant	Intron 3 of 6	1	NM_001292034.3	ENSP00000490618.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54443 AN: 151902 Hom.: 10103 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54494 AN: 152020 Hom.: 10120 Cov.: 32 AF XY: 0.362 AC XY: 26882 AN XY: 74312

African (AFR) AF: 0.283 AC: 11731 AN: 41482

American (AMR) AF: 0.425 AC: 6490 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3114 AN: 5172

South Asian (SAS) AF: 0.403 AC: 1939 AN: 4808

European-Finnish (FIN) AF: 0.370 AC: 3906 AN: 10546

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24781 AN: 67972

Other (OTH) AF: 0.390 AC: 822 AN: 2106

Alfa AF: 0.266 Hom.: 932

Bravo AF: 0.365

Asia WGS AF: 0.552 AC: 1914 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.34
PhyloP100		-0.079
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9373589; hg19: chr6-149707288;