6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAG

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP3BP6_ModerateBS2_Supporting

The ENST00000392092.7(TBP):c.246_281delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln83_Gln94del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000105 in 1,405,182 control chromosomes in the GnomAD database, including 3 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., cov: 21)

Exomes 𝑓: 0.00011 ( 3 hom. )

Consequence

TBP
ENST00000392092.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.03

Publications

4 publications found

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]

TBP Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 17
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000392092.7

BP6

Variant 6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-A is Benign according to our data. Variant chr6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-A is described in ClinVar as Benign. ClinVar VariationId is 2657160.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 13 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392092.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBP	NM_003194.5	MANE Select	c.246_281delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln83_Gln94del	disruptive_inframe_deletion	Exon 3 of 8	NP_003185.1
	TBP	NM_001172085.2		c.186_221delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln63_Gln74del	disruptive_inframe_deletion	Exon 2 of 7	NP_001165556.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TBP	ENST00000392092.7	TSL:1 MANE Select	c.246_281delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln83_Gln94del	disruptive_inframe_deletion	Exon 3 of 8	ENSP00000375942.2
TBP	ENST00000230354.10	TSL:1	c.246_281delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln83_Gln94del	disruptive_inframe_deletion	Exon 3 of 8	ENSP00000230354.5
TBP	ENST00000421512.5	TSL:1	c.246_281delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln83_Gln94del	disruptive_inframe_deletion	Exon 3 of 5	ENSP00000400008.1

Frequencies

GnomAD3 genomes

AF:

0.0000907

AC:

AN:

143372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00151

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000106

AC:

134

AN:

1261704

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

630696

show subpopulations

African (AFR)

AF:

0.000348

AC:

AN:

28776

American (AMR)

AF:

0.0000239

AC:

AN:

41894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23728

East Asian (EAS)

AF:

0.00

AC:

AN:

38406

South Asian (SAS)

AF:

0.00124

AC:

101

AN:

81728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46476

Middle Eastern (MID)

AF:

0.000202

AC:

AN:

4954

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

941844

Other (OTH)

AF:

0.0000371

AC:

AN:

53898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000906

AC:

AN:

143478

Hom.:

Cov.:

AF XY:

0.0000714

AC XY:

AN XY:

70064

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

39244

American (AMR)

AF:

0.00

AC:

AN:

14660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3200

East Asian (EAS)

AF:

0.00

AC:

AN:

4916

South Asian (SAS)

AF:

0.00151

AC:

AN:

4628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63756

Other (OTH)

AF:

0.00

AC:

AN:

1998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.0

Mutation Taster

=136/64

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over