22-41146749-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001429.4(EP300):c.2064A>G(p.Leu688Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,614,102 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L688L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 13 hom. )

Consequence

EP300
NM_001429.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.97

Publications

6 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 links:

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

EP300-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 22-41146749-A-G is Benign according to our data. Variant chr22-41146749-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.97 with no splicing effect.

BS2

High AC in GnomAd4 at 422 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.2064A>G	p.Leu688Leu	synonymous_variant	Exon 11 of 31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2 link	c.2054-1088A>G		intron_variant	Intron 10 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.2064A>G	p.Leu688Leu	synonymous_variant	Exon 11 of 31	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

422

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00307

AC:

772

AN:

251406

AF XY:

0.00310

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00724

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00452

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00367

AC:

5358

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

2746

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33476

American (AMR)

AF:

0.00206

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00777

AC:

203

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00231

AC:

199

AN:

86250

European-Finnish (FIN)

AF:

0.000711

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00406

AC:

4513

AN:

1111904

Other (OTH)

AF:

0.00366

AC:

221

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

271

542

813

1084

1355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.00277

AC:

422

AN:

152346

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41586

American (AMR)

AF:

0.00222

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00416

AC:

283

AN:

68036

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00447

Hom.:

Bravo

AF:

0.00300

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00611

EpiControl

AF:

0.00593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EP300: BP4, BP7, BS1

not specified

Benign:2

May 14, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Apr 19, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EP300-related disorder

Benign:1

Apr 29, 2019

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).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.13

(source)

DANN

Benign

0.57

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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