rs20554

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001429.4(EP300):c.3348G>A(p.Gln1116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,112 control chromosomes in the GnomAD database, including 1,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 411 hom., cov: 31)

Exomes 𝑓: 0.0089 ( 915 hom. )

Consequence

EP300
NM_001429.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.350

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 22-41157255-G-A is Benign according to our data. Variant chr22-41157255-G-A is described in ClinVar as [Benign]. Clinvar id is 158562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4 linkuse as main transcript	c.3348G>A	p.Gln1116=	synonymous_variant	18/31	ENST00000263253.9
EP300	NM_001362843.2 linkuse as main transcript	c.3270G>A	p.Gln1090=	synonymous_variant	17/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9 linkuse as main transcript	c.3348G>A	p.Gln1116=	synonymous_variant	18/31	1	NM_001429.4	P2

Frequencies

GnomAD3 genomes

AF:

0.0404

AC:

6139

AN:

152128

Hom.:

410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0254

AC:

6384

AN:

251408

Hom.:

546

AF XY:

0.0218

AC XY:

2956

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.00630

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.218

Gnomad SAS exome

AF:

0.00653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00888

AC:

12980

AN:

1461866

Hom.:

915

Cov.:

AF XY:

0.00851

AC XY:

6188

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.00749

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.00757

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000330

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0404

AC:

6146

AN:

152246

Hom.:

411

Cov.:

AF XY:

0.0399

AC XY:

2971

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.0142

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.0332

Alfa

AF:

0.00867

Hom.:

154

Bravo

AF:

0.0443

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

Cadd

Benign

1.2

Dann

Benign

0.57

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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