NM_001429.4:c.3348G>A

Variant names:

• chr22-41157255-G-A
• rs20554
• NM_001429.4:c.3348G>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.3348G>A​(p.Gln1116Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,112 control chromosomes in the GnomAD database, including 1,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (411 hom., cov: 31)
  • Exomes 𝑓: 0.0089 (915 hom.)
• Consequence: EP300 NM_001429.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.350
• Publications: 16 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=-0.49).
• BP6: Variant 22-41157255-G-A is Benign according to our data. Variant chr22-41157255-G-A is described in ClinVar as Benign. ClinVar VariationId is 158562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 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.3348G>A	p.Gln1116Gln	synonymous	Exon 18 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.3270G>A	p.Gln1090Gln	synonymous	Exon 17 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.3348G>A	p.Gln1116Gln	synonymous	Exon 18 of 31	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.3348G>A	p.Gln1116Gln	synonymous	Exon 18 of 31	ENSP00000586141.1
	EP300	ENST00000715703.1		c.3348G>A	p.Gln1116Gln	synonymous	Exon 18 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6139 AN: 152128 Hom.: 410 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0335

GnomAD2 exomes AF: 0.0254 AC: 6384 AN: 251408 AF XY: 0.0218

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.00630

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000466

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.00888 AC: 12980 AN: 1461866 Hom.: 915 Cov.: 33 AF XY: 0.00851 AC XY: 6188 AN XY: 727238

African (AFR) AF: 0.115 AC: 3838 AN: 33478

American (AMR) AF: 0.00749 AC: 335 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26134

East Asian (EAS) AF: 0.166 AC: 6569 AN: 39690

South Asian (SAS) AF: 0.00757 AC: 653 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.000330 AC: 367 AN: 1112006

Other (OTH) AF: 0.0193 AC: 1163 AN: 60390

GnomAD4 genome AF: 0.0404 AC: 6146 AN: 152246 Hom.: 411 Cov.: 31 AF XY: 0.0399 AC XY: 2971 AN XY: 74458

African (AFR) AF: 0.114 AC: 4718 AN: 41534

American (AMR) AF: 0.0142 AC: 217 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5176

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68018

Other (OTH) AF: 0.0332 AC: 70 AN: 2110

Alfa AF: 0.0147 Hom.: 409

Bravo AF: 0.0443

Asia WGS AF: 0.0800 AC: 279 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		0.35
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=93/7	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: rs20554; hg19: chr22-41553259; COSMIC: COSV54329375; COSMIC: COSV54329375;