rs7758080

Positions:

• chr6-149255943-A-G
• chr6-149255943-A-T

Variant summary

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

The NM_001292035.3(TAB2):​c.6+37167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,108 control chromosomes in the GnomAD database, including 7,830 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 0.31 (7830 hom., cov: 32)
• Consequence: TAB2 NM_001292035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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:):

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 = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAB2	NM_001292035.3	c.6+37167A>G		intron_variant			NP_001278964.1
TAB2-AS1	NR_149096.1	n.168+1441T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000606202.1	c.-121+37167A>G		intron_variant		4		ENSP00000476139.1
TAB2-AS1	ENST00000424421.2	n.168+1441T>C		intron_variant		5
TAB2-AS1	ENST00000637865.1	n.161-603T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47671 AN: 151990 Hom.: 7823 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.314 AC: 47710 AN: 152108 Hom.: 7830 Cov.: 32 AF XY: 0.312 AC XY: 23213 AN XY: 74374

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.338

Alfa AF: 0.288 Hom.: 8745

Bravo AF: 0.325

Asia WGS AF: 0.388 AC: 1346 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	13
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7758080; hg19: chr6-149577079;