rs9404034

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001292034.3(TAB2):​c.1604-6757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00024 ( 0 hom., cov: 31)

Consequence

TAB2
NM_001292034.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000243 (37/152006) while in subpopulation NFE AF= 0.000206 (14/67964). AF 95% confidence interval is 0.000124. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAB2NM_001292034.3 linkuse as main transcriptc.1604-6757G>A intron_variant ENST00000637181.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAB2ENST00000637181.2 linkuse as main transcriptc.1604-6757G>A intron_variant 1 NM_001292034.3 P1Q9NYJ8-1

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152006
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00548
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152006
Hom.:
0
Cov.:
31
AF XY:
0.000229
AC XY:
17
AN XY:
74236
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00548
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000609
Hom.:
55

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
4.0
DANN
Benign
0.45

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9404034; hg19: chr6-149711983; API