20-62009692-C-T

Variant names:

• chr20-62009692-C-T
• rs11697597
• NM_003185.4:c.1761+354G>A

Variant summary

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

The NM_003185.4(TAF4):​c.1761+354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,910 control chromosomes in the GnomAD database, including 27,785 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 0.60 (27785 hom., cov: 32)
• Consequence: TAF4 NM_003185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895
• Publications: 3 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: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF4	NM_003185.4	c.1761+354G>A		intron_variant	Intron 4 of 14	ENST00000252996.9	NP_003176.2
TAF4	XM_047440429.1	c.645+354G>A		intron_variant	Intron 5 of 15		XP_047296385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF4	ENST00000252996.9	c.1761+354G>A		intron_variant	Intron 4 of 14	1	NM_003185.4	ENSP00000252996.3
TAF4	ENST00000486599.1	n.88+354G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91098 AN: 151788 Hom.: 27784 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.600 AC: 91118 AN: 151910 Hom.: 27785 Cov.: 32 AF XY: 0.602 AC XY: 44677 AN XY: 74236

African (AFR) AF: 0.483 AC: 19991 AN: 41394

American (AMR) AF: 0.589 AC: 8995 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2419 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3309 AN: 5162

South Asian (SAS) AF: 0.574 AC: 2761 AN: 4806

European-Finnish (FIN) AF: 0.653 AC: 6892 AN: 10556

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44514 AN: 67932

Other (OTH) AF: 0.639 AC: 1348 AN: 2108

Alfa AF: 0.522 Hom.: 2199

Bravo AF: 0.591

Asia WGS AF: 0.621 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.65
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11697597; hg19: chr20-60584748;