chr22-41117770-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001429.4(EP300):c.678C>G(p.Gly226Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,220 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 29 hom. )

Consequence

EP300
NM_001429.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.116

Publications

3 publications found

Variant links:

COSMIC-nc: COSV54327274

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 Gene-Disease associations (from GenCC):

Rubinstein-Taybi syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: LIMITED Submitted by: G2P

EP300 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=-0.54).

BP6

Variant 22-41117770-C-G is Benign according to our data. Variant chr22-41117770-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 341781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.116 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00194 (296/152344) while in subpopulation EAS AF = 0.0191 (99/5194). AF 95% confidence interval is 0.016. There are 2 homozygotes in GnomAd4. There are 167 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 296 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.678C>G	p.Gly226Gly	synonymous_variant	Exon 2 of 31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2 link	c.678C>G	p.Gly226Gly	synonymous_variant	Exon 2 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.678C>G	p.Gly226Gly	synonymous_variant	Exon 2 of 31	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0192

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000705

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00258

AC:

648

AN:

251276

AF XY:

0.00262

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.00310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00191

AC:

2787

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1519

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.00335

AC:

150

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0319

AC:

1268

AN:

39700

South Asian (SAS)

AF:

0.00434

AC:

374

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00625

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000722

AC:

803

AN:

1112006

Other (OTH)

AF:

0.00214

AC:

129

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

200

401

601

802

1002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.00194

AC:

296

AN:

152344

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41576

American (AMR)

AF:

0.00621

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0191

AC:

AN:

5194

South Asian (SAS)

AF:

0.00352

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000706

AC:

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00167

Hom.:

Bravo

AF:

0.00235

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00184

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EP300: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 09, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

EP300-related disorder

Benign:1

May 02, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Jan 24, 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

-0.54

CADD

Benign

9.5

(source)

DANN

Benign

0.66

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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