6-170568356-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003194.5(TBP):​c.678-1256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,018 control chromosomes in the GnomAD database, including 11,690 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 0.38 ( 11690 hom., cov: 32)

Consequence

TBP
NM_003194.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.211
Variant links:
Genes affected
TBP (HGNC:11588): (TATA-box binding protein) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes TBP, the TATA-binding protein. A distinctive feature of TBP is a long string of glutamines in the N-terminus. This region of the protein modulates the DNA binding activity of the C terminus, and modulation of DNA binding affects the rate of transcription complex formation and initiation of transcription. The number of CAG repeats encoding the polyglutamine tract is usually 25-42, and expansion of the number of repeats to 45-66 increases the length of the polyglutamine string and is associated with spinocerebellar ataxia 17, a neurodegenerative disorder classified as a polyglutamine disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBPNM_003194.5 linkc.678-1256A>G intron_variant Intron 5 of 7 ENST00000392092.7 NP_003185.1 P20226-1Q32MN7
TBPNM_001172085.2 linkc.618-1256A>G intron_variant Intron 4 of 6 NP_001165556.1 P20226-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBPENST00000392092.7 linkc.678-1256A>G intron_variant Intron 5 of 7 1 NM_003194.5 ENSP00000375942.2 P20226-1
TBPENST00000230354.10 linkc.678-1256A>G intron_variant Intron 5 of 7 1 ENSP00000230354.5 P20226-1
TBPENST00000540980.5 linkc.618-1256A>G intron_variant Intron 4 of 6 2 ENSP00000442132.1 P20226-2
TBPENST00000636632.1 linkn.*210+851A>G intron_variant Intron 5 of 7 5 ENSP00000490461.1 A0A1B0GVC6

Frequencies

GnomAD3 genomes
AF:
0.380
AC:
57666
AN:
151900
Hom.:
11673
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.280
Gnomad AMI
AF:
0.610
Gnomad AMR
AF:
0.365
Gnomad ASJ
AF:
0.322
Gnomad EAS
AF:
0.772
Gnomad SAS
AF:
0.418
Gnomad FIN
AF:
0.438
Gnomad MID
AF:
0.331
Gnomad NFE
AF:
0.402
Gnomad OTH
AF:
0.389
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.380
AC:
57721
AN:
152018
Hom.:
11690
Cov.:
32
AF XY:
0.384
AC XY:
28541
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.280
Gnomad4 AMR
AF:
0.366
Gnomad4 ASJ
AF:
0.322
Gnomad4 EAS
AF:
0.772
Gnomad4 SAS
AF:
0.416
Gnomad4 FIN
AF:
0.438
Gnomad4 NFE
AF:
0.402
Gnomad4 OTH
AF:
0.392
Alfa
AF:
0.391
Hom.:
6077
Bravo
AF:
0.378
Asia WGS
AF:
0.564
AC:
1959
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
2.0
DANN
Benign
0.31

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: rs13207114; hg19: chr6-170877444; API