rs35560602

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001429.4(EP300):c.2499G>A(p.Ser833Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,613,596 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S833S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.016 ( 57 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 63 hom. )

Consequence

EP300
NM_001429.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.189

Publications

2 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

new If you want to explore the variant's impact on the transcript NM_001429.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 22-41149880-G-A is Benign according to our data. Variant chr22-41149880-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.189 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 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.2499G>A	p.Ser833Ser	synonymous	Exon 14 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.2421G>A	p.Ser807Ser	synonymous	Exon 13 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.2499G>A	p.Ser833Ser	synonymous	Exon 14 of 31	ENSP00000263253.7	Q09472
EP300	ENST00000916082.1		c.2499G>A	p.Ser833Ser	synonymous	Exon 14 of 31	ENSP00000586141.1
EP300	ENST00000715703.1		c.2499G>A	p.Ser833Ser	synonymous	Exon 14 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2362

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00558

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000838

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00418

AC:

1050

AN:

251346

AF XY:

0.00314

show subpopulations

Gnomad AFR exome

AF:

0.0551

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00170

AC:

2485

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1091

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0558

AC:

1868

AN:

33478

American (AMR)

AF:

0.00342

AC:

153

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000162

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000169

AC:

188

AN:

1112004

Other (OTH)

AF:

0.00391

AC:

236

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

147

294

441

588

735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.0156

AC:

2370

AN:

151732

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1143

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.0542

AC:

2241

AN:

41314

American (AMR)

AF:

0.00558

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000419

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67948

Other (OTH)

AF:

0.0119

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

109

218

327

436

545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00563

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Colorectal cancer;C3150941:Rubinstein-Taybi syndrome due to EP300 haploinsufficiency;C4551859:Rubinstein-Taybi syndrome due to CREBBP mutations;C5193035:Menke-Hennekam syndrome 2 (1)

not specified (1)

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.2

(source)

DANN

Benign

0.63

PhyloP100

-0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=73/27

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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