dbSNP rs17433014: EP300:c.94+10720G>A (chr22-41103818-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001429.4(EP300):c.94+10720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 152,278 control chromosomes in the GnomAD database, including 110 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 0.030 ( 110 hom., cov: 32)

Consequence

EP300
NM_001429.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.898

Publications

1 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=-0.88).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0301 (4590/152278) while in subpopulation NFE AF = 0.039 (2651/68026). AF 95% confidence interval is 0.0377. There are 110 homozygotes in GnomAd4. There are 2314 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4590 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.94+10720G>A		intron_variant	Intron 1 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2 link	c.94+10720G>A		intron_variant	Intron 1 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EP300	ENST00000263253.9 link	c.94+10720G>A	intron_variant	Intron 1 of 30	1	NM_001429.4	ENSP00000263253.7
EP300	ENST00000715703.1 link	c.94+10720G>A	intron_variant	Intron 1 of 30			ENSP00000520505.1
EP300	ENST00000674155.1 link	c.94+10720G>A	intron_variant	Intron 1 of 29			ENSP00000501078.1
EP300	ENST00000703544.1 link	n.94+10720G>A	intron_variant	Intron 1 of 29			ENSP00000515365.1

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4594

AN:

152160

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00671

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0261

Gnomad ASJ

AF:

0.0623

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0390

Gnomad OTH

AF:

0.0330

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

GnomAD4 genome

AF:

0.0301

AC:

4590

AN:

152278

Hom.:

110

Cov.:

AF XY:

0.0311

AC XY:

2314

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00669

AC:

278

AN:

41568

American (AMR)

AF:

0.0259

AC:

396

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0623

AC:

216

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0128

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0839

AC:

890

AN:

10604

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0390

AC:

2651

AN:

68026

Other (OTH)

AF:

0.0327

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

223

446

668

891

1114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0200

Hom.:

Bravo

AF:

0.0257

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.0

(source)

DANN

Benign

0.60

PhyloP100

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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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