6-149245689-A-G

Position:

• chr6-149245689-A-G

Variant summary

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

The NR_149096.1(TAB2-AS1):​n.169-1688T>C variant causes a intron, non coding transcript 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-AS1 NR_149096.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

Genes affected

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

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=-0.96).
• 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/exons	MANE	UniProt
TAB2-AS1	NR_149096.1	n.169-1688T>C		intron_variant, non_coding_transcript_variant
TAB2	NM_001292035.3	c.6+26913A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB2-AS1	ENST00000424421.2	n.169-1688T>C		intron_variant, non_coding_transcript_variant		5
TAB2	ENST00000606202.1	c.-121+26913A>G		intron_variant		4

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 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 1.00

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

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.538

Alfa AF: 0.533 Hom.: 42355

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

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;