Genetic Variant ENST00000451095.5:n.174G>A (chr6-149218637-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

ENSG00000228408
ENST00000451095.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.785

Variant links:

Genes affected

ENSG00000228408 (HGNC:):

ENSG00000228408 links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
TAB2	NM_001292035.3 link	c.-134G>A		5_prime_UTR_variant	Exon 2 of 7		NP_001278964.1	Q9NYJ8B4DIR9
TAB2	NR_125861.2 link	n.174G>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000228408	ENST00000451095.5 link	n.174G>A	non_coding_transcript_exon_variant	Exon 2 of 3	1
ENSG00000228408	ENST00000443992.1 link	n.99G>A	non_coding_transcript_exon_variant	Exon 2 of 3	2
ENSG00000228408	ENST00000635954.1 link	n.164G>A	non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34001

AN:

152046

Hom.:

4235

Cov.:

show subpopulations

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.:

AF XY:

0.270

AC XY:

37125

AN XY:

137332

show subpopulations

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.:

AF XY:

0.221

AC XY:

16428

AN XY:

74390

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over