20-62009692-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TAF4	NM_003185.4	c.1761+354G>A		intron_variant		ENST00000252996.9
TAF4	XM_047440429.1	c.645+354G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF4	ENST00000252996.9	c.1761+354G>A		intron_variant		1	NM_003185.4	P1
TAF4	ENST00000486599.1	n.88+354G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.639

Alfa AF: 0.523 Hom.: 2092

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

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: rs11697597; hg19: chr20-60584748;