20-61976327-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003185.4(TAF4):c.3099C>T(p.Gly1033=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,442 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: TAF4 NM_003185.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.721

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 20-61976327-G-A is Benign according to our data. Variant chr20-61976327-G-A is described in ClinVar as [Benign]. Clinvar id is 730519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.721 with no splicing effect.
• BS2: High AC in GnomAd at 255 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF4	NM_003185.4	c.3099C>T	p.Gly1033=	synonymous_variant	15/15	ENST00000252996.9
TAF4	XM_047440429.1	c.1983C>T	p.Gly661=	synonymous_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF4	ENST00000252996.9	c.3099C>T	p.Gly1033=	synonymous_variant	15/15	1	NM_003185.4	P1

Frequencies

GnomAD3 genomes AF: 0.00167 AC: 255 AN: 152250 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00182 AC: 457 AN: 250498 Hom.: 0 AF XY: 0.00175 AC XY: 237 AN XY: 135652

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00953

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00151 AC: 2211 AN: 1461074 Hom.: 3 Cov.: 31 AF XY: 0.00146 AC XY: 1061 AN XY: 726812

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00958

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.000911

GnomAD4 genome AF: 0.00167 AC: 255 AN: 152368 Hom.: 3 Cov.: 33 AF XY: 0.00189 AC XY: 141 AN XY: 74506

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.00178

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00148 Hom.: 1

Bravo AF: 0.000782

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00130

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

Invitae

Jul 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	7.7
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs150380471; hg19: chr20-60551383;