rs237026

Variant names:

• chr6-149399545-G-A
• rs237026
• NM_001292034.3:c.1939+361G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-149399545-G-A
• chr6-149399545-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292034.3(TAB2):​c.1939+361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,296 control chromosomes in the GnomAD database, including 32,173 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 0.63 (32173 hom., cov: 29)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 9 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 Gene-Disease associations (from GenCC):

• chromosome 6q24-q25 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• congenital heart defects, multiple types, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• polyvalvular heart disease syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292034.3. 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_001292034.3	MANE Select	c.1939+361G>A		intron	N/A	NP_001278963.1
	TAB2	NM_001369506.1		c.1939+361G>A		intron	N/A	NP_001356435.1
	TAB2	NM_015093.6		c.1939+361G>A		intron	N/A	NP_055908.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000637181.2	TSL:1 MANE Select	c.1939+361G>A		intron	N/A	ENSP00000490618.1
	TAB2	ENST00000470466.5	TSL:1	n.*538+361G>A		intron	N/A	ENSP00000432709.1
	TAB2	ENST00000367456.5	TSL:5	c.1939+361G>A		intron	N/A	ENSP00000356426.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94687 AN: 151178 Hom.: 32114 Cov.: 29

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.600

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 94811 AN: 151296 Hom.: 32173 Cov.: 29 AF XY: 0.628 AC XY: 46396 AN XY: 73890

African (AFR) AF: 0.901 AC: 37228 AN: 41302

American (AMR) AF: 0.587 AC: 8916 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1638 AN: 3462

East Asian (EAS) AF: 0.715 AC: 3642 AN: 5096

South Asian (SAS) AF: 0.589 AC: 2826 AN: 4800

European-Finnish (FIN) AF: 0.538 AC: 5590 AN: 10390

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33203 AN: 67748

Other (OTH) AF: 0.605 AC: 1266 AN: 2094

Alfa AF: 0.563 Hom.: 3230

Bravo AF: 0.645

Asia WGS AF: 0.725 AC: 2497 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.24
PhyloP100		0.057
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs237026; hg19: chr6-149720681;