dbSNP rs4822006: EP300:c.730-2506T>C (chr22-41123358-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001429.4(EP300):c.730-2506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,036 control chromosomes in the GnomAD database, including 28,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 28789 hom., cov: 32)

Consequence

EP300
NM_001429.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.382

Publications

10 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 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.730-2506T>C		intron_variant	Intron 2 of 30	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.730-2506T>C		intron_variant	Intron 2 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9 link	c.730-2506T>C		intron_variant	Intron 2 of 30	1	NM_001429.4	ENSP00000263253.7		Q09472

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92533

AN:

151918

Hom.:

28770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.747

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.807

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.640

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.609

AC:

92588

AN:

152036

Hom.:

28789

Cov.:

AF XY:

0.616

AC XY:

45733

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.508

AC:

21048

AN:

41462

American (AMR)

AF:

0.747

AC:

11419

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2164

AN:

3472

East Asian (EAS)

AF:

0.807

AC:

4168

AN:

5164

South Asian (SAS)

AF:

0.696

AC:

3360

AN:

4826

European-Finnish (FIN)

AF:

0.596

AC:

6279

AN:

10544

Middle Eastern (MID)

AF:

0.551

AC:

161

AN:

292

European-Non Finnish (NFE)

AF:

0.618

AC:

41991

AN:

67974

Other (OTH)

AF:

0.634

AC:

1338

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1820

3640

5459

7279

9099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.617

Hom.:

15025

Bravo

AF:

0.619

Asia WGS

AF:

0.690

AC:

2398

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.58

(source)

DANN

Benign

0.54

PhyloP100

0.38

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over