rs11095197

Positions:

• chrX-30958830-C-T

Variant summary

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

The ENST00000378933.5(TAB3):​c.-476+16183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 110,961 control chromosomes in the GnomAD database, including 3,547 homozygotes. There are 8,351 hemizygotes in GnomAD. 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 0.27 (3547 hom., 8351 hem., cov: 22)
• Consequence: TAB3 ENST00000378933.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

Genes affected

TAB3 (HGNC:30681): (TGF-beta activated kinase 1 (MAP3K7) binding protein 3) The product of this gene functions in the NF-kappaB signal transduction pathway. The encoded protein, and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent MAP3K7/TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor. The human genome contains a related pseudogene. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB3	ENST00000378932.6	c.-476+16183G>A		intron_variant		1
TAB3	ENST00000378933.5	c.-476+16183G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 29837 AN: 110906 Hom.: 3550 Cov.: 22 AF XY: 0.252 AC XY: 8334 AN XY: 33104

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.269 AC: 29842 AN: 110961 Hom.: 3547 Cov.: 22 AF XY: 0.252 AC XY: 8351 AN XY: 33169

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.233

Alfa AF: 0.228 Hom.: 4692

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs11095197; hg19: chrX-30976947; COSMIC: COSV55835076;