22-41142107-C-G

Variant names:

• chr22-41142107-C-G
• rs4820429
• NM_001429.4:c.2053+885C>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+885C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,116 control chromosomes in the GnomAD database, including 40,996 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 0.73 (40996 hom., cov: 32)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.2053+885C>G		intron_variant	Intron 10 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.2053+885C>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+885C>G		intron_variant	Intron 10 of 30	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110938 AN: 151996 Hom.: 40936 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.730 AC: 111056 AN: 152116 Hom.: 40996 Cov.: 32 AF XY: 0.735 AC XY: 54669 AN XY: 74374

African (AFR) AF: 0.689 AC: 28582 AN: 41468

American (AMR) AF: 0.830 AC: 12701 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2459 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5165 AN: 5188

South Asian (SAS) AF: 0.810 AC: 3900 AN: 4816

European-Finnish (FIN) AF: 0.685 AC: 7240 AN: 10574

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48460 AN: 67992

Other (OTH) AF: 0.774 AC: 1633 AN: 2110

Alfa AF: 0.703 Hom.: 4676

Bravo AF: 0.742

Asia WGS AF: 0.892 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.33
PhyloP100		0.16
Mutation Taster		=100/0	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: rs4820429; hg19: chr22-41538111;