rs17750066

Positions:

• chr20-62001139-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011529123.2(LOC105372704):​c.667+8A>G variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.048 (242 hom., cov: 33)
• Consequence: LOC105372704 XM_011529123.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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]

LOC105372704 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF4	NM_003185.4	c.2487-418A>G		intron_variant		ENST00000252996.9	NP_003176.2
LOC105372704	XM_011529123.2	c.667+8A>G		splice_region_variant, intron_variant			XP_011527425.1
TAF4	XM_047440429.1	c.1371-418A>G		intron_variant			XP_047296385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF4	ENST00000252996.9	c.2487-418A>G		intron_variant		1	NM_003185.4	ENSP00000252996	P1
TAF4	ENST00000488539.1	c.492-418A>G		intron_variant		5		ENSP00000476294
TAF4	ENST00000692470.1	c.363-418A>G		intron_variant, NMD_transcript_variant				ENSP00000510589
TAF4	ENST00000436129.2	n.858-418A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0434

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0263

Gnomad4 FIN AF: 0.0840

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0650 Hom.: 383

Bravo AF: 0.0440

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs17750066; hg19: chr20-60576195;