Variant rs9611506 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001429.4(EP300):c.2131+18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,605,846 control chromosomes in the GnomAD database, including 1,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 88 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1216 hom. )

Consequence

EP300
NM_001429.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0920

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 (BayesDel_noAF=-0.81).

BP6

Variant 22-41146834-T-A is Benign according to our data. Variant chr22-41146834-T-A is described in ClinVar as [Benign]. Clinvar id is 93733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41146834-T-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0776 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.2131+18T>A		intron_variant		ENST00000263253.9
EP300	NM_001362843.2 linkuse as main transcript	c.2054-1003T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9 linkuse as main transcript	c.2131+18T>A		intron_variant		1	NM_001429.4	P2

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3923

AN:

151682

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00619

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0205

Gnomad ASJ

AF:

0.0217

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0837

Gnomad FIN

AF:

0.0377

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.0345

GnomAD3 exomes

AF:

0.0347

AC:

8483

AN:

244412

Hom.:

243

AF XY:

0.0392

AC XY:

5200

AN XY:

132542

show subpopulations

Gnomad AFR exome

AF:

0.00567

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0226

Gnomad EAS exome

AF:

0.00247

Gnomad SAS exome

AF:

0.0890

Gnomad FIN exome

AF:

0.0352

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0337

GnomAD4 exome

AF:

0.0360

AC:

52367

AN:

1454046

Hom.:

1216

Cov.:

AF XY:

0.0379

AC XY:

27456

AN XY:

723646

show subpopulations

Gnomad4 AFR exome

AF:

0.00581

Gnomad4 AMR exome

AF:

0.0153

Gnomad4 ASJ exome

AF:

0.0236

Gnomad4 EAS exome

AF:

0.00147

Gnomad4 SAS exome

AF:

0.0875

Gnomad4 FIN exome

AF:

0.0389

Gnomad4 NFE exome

AF:

0.0352

Gnomad4 OTH exome

AF:

0.0335

GnomAD4 genome

AF:

0.0258

AC:

3922

AN:

151800

Hom.:

Cov.:

AF XY:

0.0267

AC XY:

1981

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.00617

Gnomad4 AMR

AF:

0.0205

Gnomad4 ASJ

AF:

0.0217

Gnomad4 EAS

AF:

0.00271

Gnomad4 SAS

AF:

0.0844

Gnomad4 FIN

AF:

0.0377

Gnomad4 NFE

AF:

0.0347

Gnomad4 OTH

AF:

0.0337

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0225

Asia WGS

AF:

0.0220

AC:

AN:

3476

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	Eurofins Ntd Llc (ga)	Apr 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.26

DANN

Benign

0.32

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