rs587778260

chr22-41178297-G-Achr22-41178297-G-C

Variant summary

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

The NM_001429.4(EP300):c.6586G>A(p.Gly2196Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EP300 NM_001429.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.03

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]

(HGNC:):

EP300-AS1 (HGNC:50504): (EP300 antisense RNA 1)

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	UniProt
EP300	NM_001429.4	c.6586G>A	p.Gly2196Arg	missense_variant	31/31	ENST00000263253.9
EP300	NM_001362843.2	c.6508G>A	p.Gly2170Arg	missense_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9	c.6586G>A	p.Gly2196Arg	missense_variant	31/31	1	NM_001429.4	P2
	ENST00000415054.1	n.82+4766C>T		intron_variant, non_coding_transcript_variant		3
EP300-AS1	ENST00000420537.1	n.224-3473C>T		intron_variant, non_coding_transcript_variant		3
EP300	ENST00000674155.1	c.6508G>A	p.Gly2170Arg	missense_variant	30/30			A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	23
Dann	Benign	0.82
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	0.077
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.93	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.28
Sift	Benign	0.064	T
Sift4G	Uncertain	0.059	T
Polyphen		0.74	P
Vest4		0.55
MutPred		0.26		Gain of MoRF binding (P = 0.0141);
MVP		0.81
ClinPred		0.34	T
GERP RS		5.2
Varity_R		0.080
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs587778260; hg19: chr22-41574301;