rs2272901

chr6-149218637-G-A

Variant summary

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

The ENST00000451095.5(ENSG00000228408):n.174G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 395,378 control chromosomes in the GnomAD database, including 13,419 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 0.22 (4232 hom., cov: 32)
  • Exomes 𝑓: 0.27 (9187 hom.)
• Consequence: ENST00000451095.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785

Genes affected

(HGNC:):

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAB2	NM_001292035.3	c.-134G>A		5_prime_UTR_variant	2/7
TAB2	NR_125861.2	n.174G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000451095.5	n.174G>A		non_coding_transcript_exon_variant	2/3	1
	ENST00000635954.1	n.164G>A		non_coding_transcript_exon_variant	2/4	5
	ENST00000443992.1	n.99G>A		non_coding_transcript_exon_variant	2/3	2
TAB2	ENST00000606202.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34001 AN: 152046 Hom.: 4235 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.266 AC: 64732 AN: 243214 Hom.: 9187 Cov.: 0 AF XY: 0.270 AC XY: 37125 AN XY: 137332

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.223 AC: 33994 AN: 152164 Hom.: 4232 Cov.: 32 AF XY: 0.221 AC XY: 16428 AN XY: 74390

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.239

Alfa AF: 0.266 Hom.: 5909

Bravo AF: 0.221

Asia WGS AF: 0.290 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.4
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272901; hg19: chr6-149539773;