6-149245689-A-G

Variant names:

• chr6-149245689-A-G
• rs6935566
• NM_001292035.3:c.6+26913A>G

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+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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

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

ENSG00000228408 (HGNC:):

ACMG classification

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	c.6+26913A>G		intron_variant	Intron 2 of 6		NP_001278964.1
TAB2-AS1	NR_149096.1	n.169-1688T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000606202.1	c.-121+26913A>G		intron_variant	Intron 1 of 1	4		ENSP00000476139.1
TAB2-AS1	ENST00000424421.2	n.169-1688T>C		intron_variant	Intron 1 of 2	5
ENSG00000228408	ENST00000635954.1	n.*135A>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81361 AN: 151630 Hom.: 22040 Cov.: 30

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: 2 AN: 4 Hom.: 1 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 2

Gnomad4 NFE exome AF: 1.00 AC: 2 AN: 2

Gnomad4 Remaining exome AC: 0 AN: 0

GnomAD4 genome AF: 0.537 AC: 81448 AN: 151748 Hom.: 22072 Cov.: 30 AF XY: 0.537 AC XY: 39798 AN XY: 74142

Gnomad4 AFR AF: 0.517 AC: 0.51655 AN: 0.51655

Gnomad4 AMR AF: 0.662 AC: 0.661925 AN: 0.661925

Gnomad4 ASJ AF: 0.435 AC: 0.435046 AN: 0.435046

Gnomad4 EAS AF: 0.569 AC: 0.568696 AN: 0.568696

Gnomad4 SAS AF: 0.481 AC: 0.480841 AN: 0.480841

Gnomad4 FIN AF: 0.531 AC: 0.531351 AN: 0.531351

Gnomad4 NFE AF: 0.529 AC: 0.528776 AN: 0.528776

Gnomad4 OTH AF: 0.538 AC: 0.537512 AN: 0.537512

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
DANN	Benign	0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6935566; hg19: chr6-149566825; COSMIC: COSV70064232;