rs603092

Positions:

• chr6-149221955-G-A

Variant summary

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

The ENST00000635954.1(ENSG00000228408):​n.303+3179G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,150 control chromosomes in the GnomAD database, including 3,402 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 0.21 (3402 hom., cov: 32)
• Consequence: ENST00000635954.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAB2	NM_001292035.3	c.6+3179G>A		intron_variant
TAB2	NR_125861.2	n.313+3179G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000635954.1	n.303+3179G>A		intron_variant, non_coding_transcript_variant		5
TAB2	ENST00000606202.1	c.-121+3179G>A		intron_variant		4
	ENST00000443992.1	n.238+3179G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000445901.1	n.79+3179G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31551 AN: 152032 Hom.: 3406 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.207 AC: 31555 AN: 152150 Hom.: 3402 Cov.: 32 AF XY: 0.206 AC XY: 15344 AN XY: 74378

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.196

Alfa AF: 0.214 Hom.: 691

Bravo AF: 0.199

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs603092; hg19: chr6-149543091;