rs4820428

chr22-41141585-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EP300	NM_001429.4	c.2053+363A>G		intron_variant		ENST00000263253.9
EP300	NM_001362843.2	c.2053+363A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9	c.2053+363A>G		intron_variant		1	NM_001429.4	P2

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0578

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.270

Alfa AF: 0.261 Hom.: 1237

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4820428; hg19: chr22-41537589;