dbSNP rs17002316: EP300:c.2380-15T>C (chr22-41149746-T-C) – ACMG Classification: Benign (-20 pts)

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.2380-15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,804 control chromosomes in the GnomAD database, including 1,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 433 hom., cov: 31)

Exomes 𝑓: 0.0092 ( 1004 hom. )

Consequence

EP300
NM_001429.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.152

Publications

7 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 (BayesDel_noAF=-0.83).

BP6

Variant 22-41149746-T-C is Benign according to our data. Variant chr22-41149746-T-C is described in ClinVar as Benign. ClinVar VariationId is 158559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 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.2380-15T>C		intron	N/A	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.2302-15T>C		intron	N/A	NP_001349772.1	A0A669KB12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EP300	ENST00000263253.9	TSL:1 MANE Select	c.2380-15T>C	intron	N/A	ENSP00000263253.7	Q09472
EP300	ENST00000916082.1		c.2380-15T>C	intron	N/A	ENSP00000586141.1
EP300	ENST00000715703.1		c.2380-15T>C	intron	N/A	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6310

AN:

152104

Hom.:

432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.0336

GnomAD2 exomes

AF:

0.0264

AC:

6633

AN:

250922

AF XY:

0.0227

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.00625

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00923

AC:

13492

AN:

1461582

Hom.:

1004

Cov.:

AF XY:

0.00885

AC XY:

6436

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.117

AC:

3907

AN:

33466

American (AMR)

AF:

0.00760

AC:

340

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000497

AC:

AN:

26132

East Asian (EAS)

AF:

0.177

AC:

7031

AN:

39698

South Asian (SAS)

AF:

0.00757

AC:

653

AN:

86244

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00728

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000329

AC:

366

AN:

1111820

Other (OTH)

AF:

0.0189

AC:

1139

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

692

1384

2075

2767

3459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.0415

AC:

6317

AN:

152222

Hom.:

433

Cov.:

AF XY:

0.0411

AC XY:

3063

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.116

AC:

4827

AN:

41492

American (AMR)

AF:

0.0145

AC:

221

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.206

AC:

1070

AN:

5182

South Asian (SAS)

AF:

0.0141

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68028

Other (OTH)

AF:

0.0332

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

280

561

841

1122

1402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0457

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.2

(source)

DANN

Benign

0.62

PhyloP100

-0.15

Mutation Taster

=100/0

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