22-41141230-G-T

Variant names:

Variant summary

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

The NM_001429.4(EP300):c.2053+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,613,534 control chromosomes in the GnomAD database, including 797,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71357 hom., cov: 33)

Exomes 𝑓: 1.0 ( 725868 hom. )

Consequence

EP300
NM_001429.4 splice_region, intron

Scores

Splicing: ADA: 0.00001963

Clinical Significance

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

Conservation

PhyloP100: -2.06

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=-0.87).

BP6

Variant 22-41141230-G-T is Benign according to our data. Variant chr22-41141230-G-T is described in ClinVar as [Benign]. Clinvar id is 93732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41141230-G-T is described in Lovd as [Likely_benign]. Variant chr22-41141230-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.2053+8G>T		splice_region_variant, intron_variant	Intron 10 of 30	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.2053+8G>T		splice_region_variant, 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.2053+8G>T		splice_region_variant, intron_variant	Intron 10 of 30	1	NM_001429.4	ENSP00000263253.7		Q09472

Frequencies

GnomAD3 genomes

AF:

0.967

AC:

147104

AN:

152202

Hom.:

71306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.980

GnomAD3 exomes

AF:

0.991

AC:

249073

AN:

251244

Hom.:

123573

AF XY:

0.994

AC XY:

134949

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.878

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.997

AC:

1456183

AN:

1461214

Hom.:

725868

Cov.:

AF XY:

0.997

AC XY:

724801

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.874

Gnomad4 AMR exome

AF:

0.996

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.993

GnomAD4 genome

AF:

0.966

AC:

147214

AN:

152320

Hom.:

71357

Cov.:

AF XY:

0.968

AC XY:

72082

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.883

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.980

Alfa

AF:

0.984

Hom.:

33201

Bravo

AF:

0.962

Asia WGS

AF:

0.994

AC:

3456

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 02, 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

- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.87

CADD

Benign

0.21

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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