rs145714752

Positions:

• chr22-41149957-T-A
• chr22-41149957-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000263253.9(EP300):​c.2576T>A​(p.Ile859Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I859T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EP300 ENST00000263253.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18214387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP300	NM_001429.4	c.2576T>A	p.Ile859Asn	missense_variant	14/31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.2498T>A	p.Ile833Asn	missense_variant	13/30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.2576T>A	p.Ile859Asn	missense_variant	14/31	1	NM_001429.4	ENSP00000263253	P2
EP300	ENST00000674155.1	c.2498T>A	p.Ile833Asn	missense_variant	13/30			ENSP00000501078	A2
EP300	ENST00000703544.1	c.*496T>A		3_prime_UTR_variant, NMD_transcript_variant	13/30			ENSP00000515365
EP300	ENST00000703545.1	c.*946T>A		3_prime_UTR_variant, NMD_transcript_variant	12/17			ENSP00000515366

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.80	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.19
Sift	Benign	0.46	T
Sift4G	Benign	0.39	T
Polyphen		0.089	B
Vest4		0.29
MutPred		0.19		Loss of sheet (P = 0.1398);
MVP		0.82
ClinPred		0.19	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.11

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: chr22-41545961;