6-149383390-G-A

Variant names:

• chr6-149383390-G-A
• rs7742990
• NM_001292034.3:c.1603+3872G>A

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+3872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,186 control chromosomes in the GnomAD database, including 57,809 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 0.87 (57809 hom., cov: 31)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	NM_001292034.3	MANE Select	c.1603+3872G>A		intron	N/A	NP_001278963.1
	TAB2	NM_001369506.1		c.1603+3872G>A		intron	N/A	NP_001356435.1
	TAB2	NM_015093.6		c.1603+3872G>A		intron	N/A	NP_055908.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000637181.2	TSL:1 MANE Select	c.1603+3872G>A		intron	N/A	ENSP00000490618.1
	TAB2	ENST00000470466.5	TSL:1	n.*202+3247G>A		intron	N/A	ENSP00000432709.1
	TAB2	ENST00000367456.5	TSL:5	c.1603+3872G>A		intron	N/A	ENSP00000356426.1

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132476 AN: 152068 Hom.: 57772 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.871 AC: 132563 AN: 152186 Hom.: 57809 Cov.: 31 AF XY: 0.871 AC XY: 64796 AN XY: 74404

African (AFR) AF: 0.824 AC: 34190 AN: 41488

American (AMR) AF: 0.888 AC: 13584 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3263 AN: 3472

East Asian (EAS) AF: 0.887 AC: 4595 AN: 5180

South Asian (SAS) AF: 0.913 AC: 4411 AN: 4832

European-Finnish (FIN) AF: 0.872 AC: 9241 AN: 10598

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60359 AN: 67994

Other (OTH) AF: 0.891 AC: 1885 AN: 2116

Alfa AF: 0.882 Hom.: 7702

Bravo AF: 0.871

Asia WGS AF: 0.884 AC: 3075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.47
PhyloP100		-1.9
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: rs7742990; hg19: chr6-149704526;