rs4822006

Variant names:

• chr22-41123358-T-C
• rs4822006
• NM_001429.4:c.730-2506T>C

Variant summary

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

The NM_001429.4(EP300):​c.730-2506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,036 control chromosomes in the GnomAD database, including 28,789 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 0.61 (28789 hom., cov: 32)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 10 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 Gene-Disease associations (from GenCC):

• Rubinstein-Taybi syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 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.730-2506T>C		intron	N/A	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.730-2506T>C		intron	N/A	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.730-2506T>C		intron	N/A	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.730-2506T>C		intron	N/A	ENSP00000586141.1
	EP300	ENST00000715703.1		c.730-2506T>C		intron	N/A	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92533 AN: 151918 Hom.: 28770 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.609 AC: 92588 AN: 152036 Hom.: 28789 Cov.: 32 AF XY: 0.616 AC XY: 45733 AN XY: 74298

African (AFR) AF: 0.508 AC: 21048 AN: 41462

American (AMR) AF: 0.747 AC: 11419 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2164 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4168 AN: 5164

South Asian (SAS) AF: 0.696 AC: 3360 AN: 4826

European-Finnish (FIN) AF: 0.596 AC: 6279 AN: 10544

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 41991 AN: 67974

Other (OTH) AF: 0.634 AC: 1338 AN: 2110

Alfa AF: 0.617 Hom.: 15025

Bravo AF: 0.619

Asia WGS AF: 0.690 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
DANN	Benign	0.54
PhyloP100		0.38
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: rs4822006; hg19: chr22-41519362;