rs1046088

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001429.4(EP300):c.6668A>C(p.Gln2223Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 1,614,146 control chromosomes in the GnomAD database, including 883 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q2223K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.023 ( 59 hom., cov: 32)

Exomes 𝑓: 0.031 ( 824 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 3.35

Publications

28 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054445565).

BP6

Variant 22-41178379-A-C is Benign according to our data. Variant chr22-41178379-A-C is described in ClinVar as [Benign]. Clinvar id is 93744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0234 (3563/152272) while in subpopulation NFE AF = 0.0357 (2427/68010). AF 95% confidence interval is 0.0345. There are 59 homozygotes in GnomAd4. There are 1701 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3563 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.6668A>C	p.Gln2223Pro	missense_variant	Exon 31 of 31	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.6590A>C	p.Gln2197Pro	missense_variant	Exon 30 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.6668A>C	p.Gln2223Pro	missense_variant	Exon 31 of 31	1	NM_001429.4	ENSP00000263253.7		Q09472

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3563

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00610

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0401

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0216

GnomAD2 exomes

AF:

0.0238

AC:

5967

AN:

251224

AF XY:

0.0235

show subpopulations

Gnomad AFR exome

AF:

0.00511

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0410

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0294

GnomAD4 exome

AF:

0.0311

AC:

45443

AN:

1461874

Hom.:

824

Cov.:

AF XY:

0.0303

AC XY:

22043

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00490

AC:

164

AN:

33480

American (AMR)

AF:

0.0145

AC:

647

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0261

AC:

682

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00326

AC:

281

AN:

86256

European-Finnish (FIN)

AF:

0.0468

AC:

2502

AN:

53420

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0354

AC:

39372

AN:

1111998

Other (OTH)

AF:

0.0290

AC:

1750

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3182

6364

9546

12728

15910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0234

AC:

3563

AN:

152272

Hom.:

Cov.:

AF XY:

0.0228

AC XY:

1701

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00609

AC:

253

AN:

41566

American (AMR)

AF:

0.0169

AC:

258

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0401

AC:

425

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0357

AC:

2427

AN:

68010

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

177

354

530

707

884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0302

Hom.:

228

Bravo

AF:

0.0214

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0332

AC:

128

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.0363

AC:

312

ExAC

AF:

0.0241

AC:

2925

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0350

EpiControl

AF:

0.0299

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2Other:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 07, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Feb 03, 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

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.082

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.76

MutationAssessor

Benign

2.0

PhyloP100

3.4

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.18

Sift

Benign

0.17

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.11

ClinPred

0.031

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.37

Mutation Taster

=95/5

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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rs1046088

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over