6-149221955-G-A

Variant names:

• chr6-149221955-G-A
• rs603092
• NM_001292035.3:c.6+3179G>A

Variant summary

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

The NM_001292035.3(TAB2):​c.6+3179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,150 control chromosomes in the GnomAD database, including 3,402 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 0.21 (3402 hom., cov: 32)
• Consequence: TAB2 NM_001292035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• 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

ENSG00000228408 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292035.3. 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_001292035.3		c.6+3179G>A		intron	N/A	NP_001278964.1
	TAB2	NR_125861.2		n.313+3179G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000606202.1	TSL:4	c.-121+3179G>A		intron	N/A	ENSP00000476139.1
	ENSG00000228408	ENST00000443992.1	TSL:2	n.238+3179G>A		intron	N/A
	ENSG00000228408	ENST00000445901.1	TSL:2	n.79+3179G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31551 AN: 152032 Hom.: 3406 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.207 AC: 31555 AN: 152150 Hom.: 3402 Cov.: 32 AF XY: 0.206 AC XY: 15344 AN XY: 74378

African (AFR) AF: 0.178 AC: 7387 AN: 41516

American (AMR) AF: 0.164 AC: 2503 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3470

East Asian (EAS) AF: 0.117 AC: 605 AN: 5184

South Asian (SAS) AF: 0.176 AC: 848 AN: 4826

European-Finnish (FIN) AF: 0.245 AC: 2585 AN: 10560

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16193 AN: 67990

Other (OTH) AF: 0.196 AC: 414 AN: 2110

Alfa AF: 0.213 Hom.: 702

Bravo AF: 0.199

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs603092; hg19: chr6-149543091;