rs146242251

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001429.4(EP300):c.1519A>G(p.Ser507Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000781 in 1,614,146 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00077 ( 6 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 3.08

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051556826).

BP6

Variant 22-41131624-A-G is Benign according to our data. Variant chr22-41131624-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 134065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41131624-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00077 (1125/1461850) while in subpopulation EAS AF= 0.0172 (681/39700). AF 95% confidence interval is 0.0161. There are 6 homozygotes in gnomad4_exome. There are 542 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 136 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.1519A>G	p.Ser507Gly	missense_variant	Exon 6 of 31	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.1519A>G	p.Ser507Gly	missense_variant	Exon 6 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.1519A>G	p.Ser507Gly	missense_variant	Exon 6 of 31	1	NM_001429.4	ENSP00000263253.7		Q09472

Frequencies

GnomAD3 genomes

AF:

0.000894

AC:

136

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00191

AC:

479

AN:

250938

Hom.:

AF XY:

0.00173

AC XY:

235

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0164

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000770

AC:

1125

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000745

AC XY:

542

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.0172

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000893

AC:

136

AN:

152296

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.0162

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000954

Hom.:

Bravo

AF:

0.00115

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00173

AC:

210

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 13, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

EP300-related disorder

Benign:1

Nov 22, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Colorectal cancer;C3150941:Rubinstein-Taybi syndrome due to EP300 haploinsufficiency;C4551859:Rubinstein-Taybi syndrome due to CREBBP mutations;C5193035:Menke-Hennekam syndrome 2

Benign:1

Aug 23, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.94

REVEL

Benign

0.22

Sift

Benign

0.035

Sift4G

Benign

0.25

Polyphen

0.014

Vest4

0.022

MVP

0.84

ClinPred

0.035

GERP RS

1.0

Varity_R

0.058

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over