rs17750066

Variant names:

• chr20-62001139-T-C
• rs17750066
• NM_003185.4:c.2487-418A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003185.4(TAF4):​c.2487-418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 152,310 control chromosomes in the GnomAD database, including 242 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 0.048 (242 hom., cov: 33)
• Consequence: TAF4 NM_003185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 4 publications found

Genes affected

TAF4 (HGNC:11537): (TATA-box binding protein associated factor 4) 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 one of the larger subunits of TFIID that has been shown to potentiate transcriptional activation by retinoic acid, thyroid hormone and vitamin D3 receptors. In addition, this subunit interacts with the transcription factor CREB, which has a glutamine-rich activation domain, and binds to other proteins containing glutamine-rich regions. Aberrant binding to this subunit by proteins with expanded polyglutamine regions has been suggested as one of the pathogenetic mechanisms underlying a group of neurodegenerative disorders referred to as polyglutamine diseases. [provided by RefSeq, Jul 2008]

TAF4 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal dominant 73

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, PanelApp Australia

LOC105372704 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003185.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4	NM_003185.4	MANE Select	c.2487-418A>G		intron	N/A	NP_003176.2	O00268

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4	ENST00000252996.9	TSL:1 MANE Select	c.2487-418A>G		intron	N/A	ENSP00000252996.3	O00268
	TAF4	ENST00000488539.1	TSL:5	c.492-418A>G		intron	N/A	ENSP00000476294.1	V9GY14
	TAF4	ENST00000436129.2	TSL:2	n.858-418A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7277 AN: 152192 Hom.: 242 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0478 AC: 7278 AN: 152310 Hom.: 242 Cov.: 33 AF XY: 0.0476 AC XY: 3543 AN XY: 74476

African (AFR) AF: 0.0127 AC: 527 AN: 41580

American (AMR) AF: 0.0434 AC: 664 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 172 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4830

European-Finnish (FIN) AF: 0.0840 AC: 891 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0708 AC: 4812 AN: 68014

Other (OTH) AF: 0.0350 AC: 74 AN: 2116

Alfa AF: 0.0588 Hom.: 613

Bravo AF: 0.0440

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17750066; hg19: chr20-60576195;