22-41176537-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001429.4(EP300):c.5061+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 1,613,432 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 57 hom., cov: 32)

Exomes 𝑓: 0.025 ( 593 hom. )

Consequence

EP300
NM_001429.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.656

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:

ENSG00000232754 (HGNC:):

ENSG00000232754 links:

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

EP300-AS1 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=-0.88).

BP6

Variant 22-41176537-C-T is Benign according to our data. Variant chr22-41176537-C-T is described in ClinVar as [Benign]. Clinvar id is 158566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41176537-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0208 (3171/152180) while in subpopulation SAS AF= 0.0338 (163/4818). AF 95% confidence interval is 0.0296. There are 57 homozygotes in gnomad4. There are 1670 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.5061+9C>T		intron_variant	Intron 30 of 30	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.4983+9C>T		intron_variant	Intron 29 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.5061+9C>T		intron_variant	Intron 30 of 30	1	NM_001429.4	ENSP00000263253.7		Q09472

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3169

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00485

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0180

Gnomad ASJ

AF:

0.0629

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0334

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0258

AC:

6445

AN:

249560

Hom.:

141

AF XY:

0.0274

AC XY:

3696

AN XY:

135006

show subpopulations

Gnomad AFR exome

AF:

0.00371

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0616

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0365

Gnomad FIN exome

AF:

0.0588

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0302

GnomAD4 exome

AF:

0.0251

AC:

36731

AN:

1461252

Hom.:

593

Cov.:

AF XY:

0.0259

AC XY:

18819

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.00436

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0599

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0375

Gnomad4 FIN exome

AF:

0.0549

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0208

AC:

3171

AN:

152180

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

1670

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00484

Gnomad4 AMR

AF:

0.0179

Gnomad4 ASJ

AF:

0.0629

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0338

Gnomad4 FIN

AF:

0.0560

Gnomad4 NFE

AF:

0.0241

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0254

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.88

CADD

Benign

0.66

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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