rs4820428

Variant names:

• chr22-41141585-A-G
• rs4820428
• NM_001429.4:c.2053+363A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001429.4(EP300):​c.2053+363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,166 control chromosomes in the GnomAD database, including 5,581 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 0.25 (5581 hom., cov: 32)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.2053+363A>G		intron_variant	Intron 10 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.2053+363A>G		intron_variant	Intron 10 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.2053+363A>G		intron_variant	Intron 10 of 30	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37910 AN: 152048 Hom.: 5570 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 37932 AN: 152166 Hom.: 5581 Cov.: 32 AF XY: 0.257 AC XY: 19137 AN XY: 74380

African (AFR) AF: 0.123 AC: 5114 AN: 41558

American (AMR) AF: 0.428 AC: 6541 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3468

East Asian (EAS) AF: 0.0578 AC: 300 AN: 5188

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4814

European-Finnish (FIN) AF: 0.318 AC: 3357 AN: 10560

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18678 AN: 67992

Other (OTH) AF: 0.270 AC: 570 AN: 2112

Alfa AF: 0.257 Hom.: 1241

Bravo AF: 0.255

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4820428; hg19: chr22-41537589;