chr22-41157255-G-A

Variant names:

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.3348G>A(p.Gln1116Gln) 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:5

Conservation

PhyloP100: 0.350

Publications

16 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=-0.49).

BP6

Variant 22-41157255-G-A is Benign according to our data. Variant chr22-41157255-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001429.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	NM_001429.4	MANE Select	c.3348G>A	p.Gln1116Gln	synonymous	Exon 18 of 31	NP_001420.2
	EP300	NM_001362843.2		c.3270G>A	p.Gln1090Gln	synonymous	Exon 17 of 30	NP_001349772.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EP300	ENST00000263253.9	TSL:1 MANE Select	c.3348G>A	p.Gln1116Gln	synonymous	Exon 18 of 31	ENSP00000263253.7
EP300	ENST00000715703.1		c.3348G>A	p.Gln1116Gln	synonymous	Exon 18 of 31	ENSP00000520505.1
EP300	ENST00000674155.1		c.3270G>A	p.Gln1090Gln	synonymous	Exon 17 of 30	ENSP00000501078.1

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

GnomAD2 exomes

AF:

0.0254

AC:

6384

AN:

251408

AF XY:

0.0218

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 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

African (AFR)

AF:

0.115

AC:

3838

AN:

33478

American (AMR)

AF:

0.00749

AC:

335

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000497

AC:

AN:

26134

East Asian (EAS)

AF:

0.166

AC:

6569

AN:

39690

South Asian (SAS)

AF:

0.00757

AC:

653

AN:

86256

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00711

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000330

AC:

367

AN:

1112006

Other (OTH)

AF:

0.0193

AC:

1163

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

693

1386

2078

2771

3464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

244

488

732

976

1220

<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:

0.0404

AC:

6146

AN:

152246

Hom.:

411

Cov.:

AF XY:

0.0399

AC XY:

2971

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.114

AC:

4718

AN:

41534

American (AMR)

AF:

0.0142

AC:

217

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.196

AC:

1013

AN:

5176

South Asian (SAS)

AF:

0.0141

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68018

Other (OTH)

AF:

0.0332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

273

546

820

1093

1366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0147

Hom.:

409

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 27, 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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.2

(source)

DANN

Benign

0.57

PhyloP100

0.35

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=93/7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over