rs11095197

Variant names:

• chrX-30958830-C-T
• rs11095197
• ENST00000378933.5:c.-476+16183G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378933.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB3	ENST00000378933.5	TSL:1	c.-476+16183G>A		intron	N/A	ENSP00000368215.1	Q8N5C8-1
	TAB3	ENST00000378932.6	TSL:1	c.-476+16183G>A		intron	N/A	ENSP00000368214.2	Q8N5C8-2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 29837 AN: 110906 Hom.: 3550 Cov.: 22

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

African (AFR) AF: 0.460 AC: 13990 AN: 30429

American (AMR) AF: 0.157 AC: 1650 AN: 10493

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 687 AN: 2637

East Asian (EAS) AF: 0.0863 AC: 304 AN: 3524

South Asian (SAS) AF: 0.189 AC: 497 AN: 2625

European-Finnish (FIN) AF: 0.166 AC: 993 AN: 5983

Middle Eastern (MID) AF: 0.190 AC: 40 AN: 211

European-Non Finnish (NFE) AF: 0.210 AC: 11106 AN: 52871

Other (OTH) AF: 0.233 AC: 352 AN: 1510

Alfa AF: 0.236 Hom.: 7334

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.47
PhyloP100		-0.69
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: rs11095197; hg19: chrX-30976947; COSMIC: COSV55835076;