rs20552

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001429.4(EP300):c.3183T>A(p.Thr1061Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,612,840 control chromosomes in the GnomAD database, including 329,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28740 hom., cov: 31)

Exomes 𝑓: 0.64 ( 300836 hom. )

Consequence

EP300
NM_001429.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.557

Publications

37 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 22-41155035-T-A is Benign according to our data. Variant chr22-41155035-T-A is described in ClinVar as Benign. ClinVar VariationId is 93738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.557 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.3183T>A	p.Thr1061Thr	synonymous_variant	Exon 17 of 31	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.3105T>A	p.Thr1035Thr	synonymous_variant	Exon 16 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.3183T>A	p.Thr1061Thr	synonymous_variant	Exon 17 of 31	1	NM_001429.4	ENSP00000263253.7		Q09472

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92405

AN:

151824

Hom.:

28721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.733

Gnomad AMR

AF:

0.746

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.639

GnomAD2 exomes

AF:

0.665

AC:

167229

AN:

251460

AF XY:

0.660

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.831

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.812

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.624

Gnomad OTH exome

AF:

0.656

GnomAD4 exome

AF:

0.639

AC:

933071

AN:

1460898

Hom.:

300836

Cov.:

AF XY:

0.639

AC XY:

464575

AN XY:

726798

show subpopulations

African (AFR)

AF:

0.492

AC:

16455

AN:

33466

American (AMR)

AF:

0.821

AC:

36700

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

16264

AN:

26132

East Asian (EAS)

AF:

0.799

AC:

31724

AN:

39694

South Asian (SAS)

AF:

0.678

AC:

58503

AN:

86248

European-Finnish (FIN)

AF:

0.610

AC:

32562

AN:

53408

Middle Eastern (MID)

AF:

0.586

AC:

3381

AN:

5766

European-Non Finnish (NFE)

AF:

0.629

AC:

698849

AN:

1111094

Other (OTH)

AF:

0.640

AC:

38633

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16818

33636

50454

67272

84090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18768

37536

56304

75072

93840

<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:

0.609

AC:

92460

AN:

151942

Hom.:

28740

Cov.:

AF XY:

0.615

AC XY:

45655

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.506

AC:

20977

AN:

41418

American (AMR)

AF:

0.747

AC:

11411

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.624

AC:

2165

AN:

3470

East Asian (EAS)

AF:

0.808

AC:

4179

AN:

5172

South Asian (SAS)

AF:

0.697

AC:

3360

AN:

4820

European-Finnish (FIN)

AF:

0.594

AC:

6249

AN:

10522

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.618

AC:

41962

AN:

67952

Other (OTH)

AF:

0.633

AC:

1334

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1803

3606

5408

7211

9014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.615

Hom.:

9393

Bravo

AF:

0.619

Asia WGS

AF:

0.689

AC:

2394

AN:

3478

EpiCase

AF:

0.625

EpiControl

AF:

0.626

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 10, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Menke-Hennekam syndrome 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.43

(source)

DANN

Benign

0.60

PhyloP100

-0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=88/12

polymorphism (auto)

(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