rs142030651

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001429.4(EP300):c.631G>A(p.Gly211Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0082 in 1,614,214 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G211D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0064 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 70 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 3.32

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

Rubinstein-Taybi syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: LIMITED Submitted by: G2P

EP300 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009073317).

BP6

Variant 22-41117723-G-A is Benign according to our data. Variant chr22-41117723-G-A is described in ClinVar as Benign. ClinVar VariationId is 134043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 968 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.631G>A	p.Gly211Ser	missense_variant	Exon 2 of 31	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.631G>A	p.Gly211Ser	missense_variant	Exon 2 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.631G>A	p.Gly211Ser	missense_variant	Exon 2 of 31	1	NM_001429.4	ENSP00000263253.7		Q09472

Frequencies

GnomAD3 genomes

AF:

0.00637

AC:

969

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00879

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00606

AC:

1524

AN:

251410

AF XY:

0.00592

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00946

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00838

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00840

AC:

12274

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

6004

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

33480

American (AMR)

AF:

0.0102

AC:

455

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

309

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00139

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00978

AC:

10877

AN:

1112006

Other (OTH)

AF:

0.00818

AC:

494

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

855

1709

2564

3418

4273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

432

864

1296

1728

2160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00635

AC:

968

AN:

152336

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

453

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00192

AC:

AN:

41582

American (AMR)

AF:

0.0142

AC:

217

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00879

AC:

598

AN:

68036

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00761

Hom.:

Bravo

AF:

0.00694

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00535

AC:

650

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EP300: BS1, BS2 -

not specified

Benign:2Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

EP300-related disorder

Benign:1

Jul 19, 2022

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 19, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Benign

0.013

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.5

PhyloP100

3.3

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.35

Sift

Benign

0.051

Sift4G

Benign

0.095

Polyphen

0.14

Vest4

0.34

MVP

0.87

ClinPred

0.014

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.081

gMVP

0.45

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over