rs1555908795

Positions:

• chr22-41141196-G-A
• chr22-41141196-G-C
• chr22-41141196-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001429.4(EP300):​c.2027G>A​(p.Gly676Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EP300 NM_001429.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.01

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP300	NM_001429.4	c.2027G>A	p.Gly676Glu	missense_variant	10/31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.2027G>A	p.Gly676Glu	missense_variant	10/30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.2027G>A	p.Gly676Glu	missense_variant	10/31	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.78	D;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	-0.081	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.1	D;.
REVEL	Uncertain	0.51
Sift	Benign	0.067	T;.
Sift4G	Benign	0.14	T;D
Polyphen		0.82	P;.
Vest4		0.92
MutPred		0.15		Gain of solvent accessibility (P = 0.2192);.;
MVP		0.85
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.32
gMVP		0.36

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-41537200; COSMIC: COSV99610101;