NM_001429.4:c.3183T>A

Variant names:

• chr22-41155035-T-A
• rs20552
• NM_001429.4:c.3183T>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001429.4(EP300):​c.3183T>A​(p.Thr1061Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,612,840 control chromosomes in the GnomAD database, including 329,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28740 hom., cov: 31)
  • Exomes 𝑓: 0.64 (300836 hom.)
• Consequence: EP300 NM_001429.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.557
• Publications: 38 publications found

Genes affected

EP300 (HGNC:3373): (E1A binding protein p300) This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer. [provided by RefSeq, Jul 2008]

EP300-AS1 (HGNC:50504): (EP300 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 22-41155035-T-A is Benign according to our data. Variant chr22-41155035-T-A is described in ClinVar as Benign. ClinVar VariationId is 93738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.557 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001429.4. 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
	EP300	NM_001429.4	MANE Select	c.3183T>A	p.Thr1061Thr	synonymous	Exon 17 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.3105T>A	p.Thr1035Thr	synonymous	Exon 16 of 30	NP_001349772.1	A0A669KB12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	ENST00000263253.9	TSL:1 MANE Select	c.3183T>A	p.Thr1061Thr	synonymous	Exon 17 of 31	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.3183T>A	p.Thr1061Thr	synonymous	Exon 17 of 31	ENSP00000586141.1
	EP300	ENST00000715703.1		c.3183T>A	p.Thr1061Thr	synonymous	Exon 17 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92405 AN: 151824 Hom.: 28721 Cov.: 31

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.639

GnomAD2 exomes AF: 0.665 AC: 167229 AN: 251460 AF XY: 0.660

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.625

Gnomad EAS exome AF: 0.812

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.656

GnomAD4 exome AF: 0.639 AC: 933071 AN: 1460898 Hom.: 300836 Cov.: 46 AF XY: 0.639 AC XY: 464575 AN XY: 726798

African (AFR) AF: 0.492 AC: 16455 AN: 33466

American (AMR) AF: 0.821 AC: 36700 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 16264 AN: 26132

East Asian (EAS) AF: 0.799 AC: 31724 AN: 39694

South Asian (SAS) AF: 0.678 AC: 58503 AN: 86248

European-Finnish (FIN) AF: 0.610 AC: 32562 AN: 53408

Middle Eastern (MID) AF: 0.586 AC: 3381 AN: 5766

European-Non Finnish (NFE) AF: 0.629 AC: 698849 AN: 1111094

Other (OTH) AF: 0.640 AC: 38633 AN: 60366

GnomAD4 genome AF: 0.609 AC: 92460 AN: 151942 Hom.: 28740 Cov.: 31 AF XY: 0.615 AC XY: 45655 AN XY: 74246

African (AFR) AF: 0.506 AC: 20977 AN: 41418

American (AMR) AF: 0.747 AC: 11411 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2165 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4179 AN: 5172

South Asian (SAS) AF: 0.697 AC: 3360 AN: 4820

European-Finnish (FIN) AF: 0.594 AC: 6249 AN: 10522

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41962 AN: 67952

Other (OTH) AF: 0.633 AC: 1334 AN: 2108

Alfa AF: 0.615 Hom.: 9393

Bravo AF: 0.619

Asia WGS AF: 0.689 AC: 2394 AN: 3478

EpiCase AF: 0.625

EpiControl AF: 0.626

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (2)
-	-	1	Menke-Hennekam syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.43
DANN	Benign	0.60
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=88/12	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: rs20552; hg19: chr22-41551039; COSMIC: COSV54326782; COSMIC: COSV54326782;