rs1491487452
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBA1
The NM_003194.5(TBP):βc.228_229delβ(p.Gln77AlafsTer100) variant causes a frameshift change. The variant allele was found at a frequency of 0.296 in 661,170 control chromosomes in the GnomAD database, including 36,712 homozygotes. Variant has been reported in ClinVar as Benign (β β ). Synonymous variant affecting the same amino acid position (i.e. Q76Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.37 ( 11016 hom., cov: 21)
Exomes π: 0.28 ( 25696 hom. )
Consequence
TBP
NM_003194.5 frameshift
NM_003194.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.78
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 -8 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
BP6
?
Variant 6-170561963-AGC-A is Benign according to our data. Variant chr6-170561963-AGC-A is described in ClinVar as [Benign]. Clinvar id is 403524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-170561963-AGC-A is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBP | NM_003194.5 | c.228_229del | p.Gln77AlafsTer100 | frameshift_variant | 3/8 | ENST00000392092.7 | |
TBP | NM_001172085.2 | c.168_169del | p.Gln57AlafsTer100 | frameshift_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBP | ENST00000392092.7 | c.228_229del | p.Gln77AlafsTer100 | frameshift_variant | 3/8 | 1 | NM_003194.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.366 AC: 48502AN: 132638Hom.: 11006 Cov.: 21
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GnomAD3 exomes AF: 0.0697 AC: 12096AN: 173514Hom.: 230 AF XY: 0.0625 AC XY: 6026AN XY: 96468
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GnomAD4 exome AF: 0.279 AC: 147219AN: 528434Hom.: 25696 AF XY: 0.289 AC XY: 78543AN XY: 271860
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GnomAD4 genome ? AF: 0.366 AC: 48553AN: 132736Hom.: 11016 Cov.: 21 AF XY: 0.356 AC XY: 22899AN XY: 64402
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at