rs237032

Positions:

• chr6-149395036-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292034.3(TAB2):​c.1604-2568A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,262 control chromosomes in the GnomAD database, including 1,336 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 (1336 hom., cov: 33)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAB2	NM_001292034.3	c.1604-2568A>G		intron_variant		ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2	c.1604-2568A>G		intron_variant		1	NM_001292034.3	ENSP00000490618	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19562 AN: 152144 Hom.: 1327 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.129 AC: 19593 AN: 152262 Hom.: 1336 Cov.: 33 AF XY: 0.129 AC XY: 9598 AN XY: 74456

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0872

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.109

Alfa AF: 0.115 Hom.: 138

Bravo AF: 0.128

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs237032; hg19: chr6-149716172;