rs1555909666

Variant names:

• chr22-41151998-G-A
• rs1555909666
• NM_001429.4:c.2983G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-41151998-G-A
• chr22-41151998-G-T
• chr22-41151998-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001429.4(EP300):​c.2983G>A​(p.Glu995Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EP300 NM_001429.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.78
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.2983G>A	p.Glu995Lys	missense	Exon 15 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.2905G>A	p.Glu969Lys	missense	Exon 14 of 30	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.2983G>A	p.Glu995Lys	missense	Exon 15 of 31	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.2983G>A	p.Glu995Lys	missense	Exon 15 of 31	ENSP00000586141.1
	EP300	ENST00000715703.1		c.2983G>A	p.Glu995Lys	missense	Exon 15 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.087
Eigen_PC	Benign	0.084
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.8
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.46
Sift	Benign	0.049	D
Sift4G	Benign	0.44	T
Polyphen		0.083	B
Vest4		0.59
MutPred		0.28		Gain of ubiquitination at E995 (P = 0.0039)
MVP		0.89
ClinPred		0.61	D
GERP RS		5.8
Varity_R		0.088
gMVP		0.26
Mutation Taster		=75/25	polymorphism

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: rs1555909666; hg19: chr22-41548002;