rs20551

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001429.4(EP300):c.2989A>G(p.Ile997Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,613,848 control chromosomes in the GnomAD database, including 71,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5329 hom., cov: 31)

Exomes 𝑓: 0.29 ( 66210 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 2.95

Publications

91 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=1.5753508E-4).

BP6

Variant 22-41152004-A-G is Benign according to our data. Variant chr22-41152004-A-G is described in ClinVar as Benign. ClinVar VariationId is 93736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.412 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	NM_001429.4	MANE Select	c.2989A>G	p.Ile997Val	missense	Exon 15 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.2911A>G	p.Ile971Val	missense	Exon 14 of 30	NP_001349772.1	A0A669KB12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EP300	ENST00000263253.9	TSL:1 MANE Select	c.2989A>G	p.Ile997Val	missense	Exon 15 of 31	ENSP00000263253.7	Q09472
EP300	ENST00000916082.1		c.2989A>G	p.Ile997Val	missense	Exon 15 of 31	ENSP00000586141.1
EP300	ENST00000715703.1		c.2989A>G	p.Ile997Val	missense	Exon 15 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35091

AN:

152024

Hom.:

5319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0585

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.0583

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.259

GnomAD2 exomes

AF:

0.310

AC:

77896

AN:

251398

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.0532

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.0626

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.279

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.289

AC:

421891

AN:

1461706

Hom.:

66210

Cov.:

AF XY:

0.291

AC XY:

211498

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.0483

AC:

1617

AN:

33480

American (AMR)

AF:

0.576

AC:

25778

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

8538

AN:

26130

East Asian (EAS)

AF:

0.0414

AC:

1644

AN:

39698

South Asian (SAS)

AF:

0.374

AC:

32238

AN:

86242

European-Finnish (FIN)

AF:

0.318

AC:

16998

AN:

53418

Middle Eastern (MID)

AF:

0.285

AC:

1646

AN:

5768

European-Non Finnish (NFE)

AF:

0.285

AC:

316463

AN:

1111860

Other (OTH)

AF:

0.281

AC:

16969

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16470

32941

49411

65882

82352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10606

21212

31818

42424

53030

<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:

0.231

AC:

35108

AN:

152142

Hom.:

5329

Cov.:

AF XY:

0.240

AC XY:

17831

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0583

AC:

2421

AN:

41530

American (AMR)

AF:

0.421

AC:

6428

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

1112

AN:

3466

East Asian (EAS)

AF:

0.0582

AC:

302

AN:

5188

South Asian (SAS)

AF:

0.374

AC:

1804

AN:

4828

European-Finnish (FIN)

AF:

0.318

AC:

3362

AN:

10562

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.275

AC:

18681

AN:

67988

Other (OTH)

AF:

0.256

AC:

540

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1272

2544

3816

5088

6360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.261

Hom.:

17612

Bravo

AF:

0.234

TwinsUK

AF:

0.298

AC:

1106

ALSPAC

AF:

0.275

AC:

1059

ESP6500AA

AF:

0.0604

AC:

266

ESP6500EA

AF:

0.280

AC:

2411

ExAC

AF:

0.296

AC:

35902

Asia WGS

AF:

0.176

AC:

613

AN:

3478

EpiCase

AF:

0.287

EpiControl

AF:

0.277

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (2)

Menke-Hennekam syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.4

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.34

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.63

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.59

MetaRNN

Benign

0.00016

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

2.9

PrimateAI

Benign

0.30

PROVEAN

Benign

0.35

REVEL

Benign

0.24

Sift

Benign

0.31

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.014

ClinPred

0.0097

GERP RS

3.6

Varity_R

0.029

gMVP

0.061

Mutation Taster

=91/9

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

Computational scores

Splicing

Publications

Other links and lift over