chr6-149245689-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
• Publications: 2 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-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.

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+26913A>G		intron	N/A	NP_001278964.1
	TAB2-AS1	NR_149096.1		n.169-1688T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000606202.1	TSL:4	c.-121+26913A>G		intron	N/A	ENSP00000476139.1
	TAB2-AS1	ENST00000424421.3	TSL:5	n.175-1688T>C		intron	N/A
	ENSG00000228408	ENST00000635954.1	TSL:5	n.*135A>G		downstream_gene	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) 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

African (AFR) AF: 0.517 AC: 21349 AN: 41330

American (AMR) AF: 0.662 AC: 10097 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1507 AN: 3464

East Asian (EAS) AF: 0.569 AC: 2914 AN: 5124

South Asian (SAS) AF: 0.481 AC: 2309 AN: 4802

European-Finnish (FIN) AF: 0.531 AC: 5593 AN: 10526

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35924 AN: 67938

Other (OTH) AF: 0.538 AC: 1132 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.38
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: rs6935566; hg19: chr6-149566825; COSMIC: COSV70064232;