6-170561488-T-G

Position:

• chr6-170561488-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003194.5(TBP):​c.55-303T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,964 control chromosomes in the GnomAD database, including 23,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (23617 hom., cov: 32)
• Consequence: TBP NM_003194.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.71

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 6-170561488-T-G is Benign according to our data. Variant chr6-170561488-T-G is described in ClinVar as [Benign]. Clinvar id is 1274220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBP	NM_003194.5	c.55-303T>G		intron_variant		ENST00000392092.7	NP_003185.1
TBP	NM_001172085.2	c.-6-303T>G		intron_variant			NP_001165556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBP	ENST00000392092.7	c.55-303T>G		intron_variant		1	NM_003194.5	ENSP00000375942	P2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83705 AN: 151846 Hom.: 23581 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.551 AC: 83787 AN: 151964 Hom.: 23617 Cov.: 32 AF XY: 0.549 AC XY: 40771 AN XY: 74262

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.546

Alfa AF: 0.514 Hom.: 9284

Bravo AF: 0.562

Asia WGS AF: 0.630 AC: 2188 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs6928833; hg19: chr6-170870576;