Menu
GeneBe

rs144787962

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_001429.4(EP300):c.6907C>G(p.Leu2303Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

2
9
8

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 4.79
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-AS1 (HGNC:50504): (EP300 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38150293).
BP6
Variant 22-41178618-C-G is Benign according to our data. Variant chr22-41178618-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 134054.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EP300NM_001429.4 linkuse as main transcriptc.6907C>G p.Leu2303Val missense_variant 31/31 ENST00000263253.9
EP300NM_001362843.2 linkuse as main transcriptc.6829C>G p.Leu2277Val missense_variant 30/30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EP300ENST00000263253.9 linkuse as main transcriptc.6907C>G p.Leu2303Val missense_variant 31/311 NM_001429.4 P2
ENST00000415054.1 linkuse as main transcriptn.82+4445G>C intron_variant, non_coding_transcript_variant 3
EP300-AS1ENST00000420537.1 linkuse as main transcriptn.224-3794G>C intron_variant, non_coding_transcript_variant 3
EP300ENST00000674155.1 linkuse as main transcriptc.6829C>G p.Leu2277Val missense_variant 30/30 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251386
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461888
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 12, 2023- -
not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.062
T
BayesDel_noAF
Benign
-0.16
Cadd
Uncertain
24
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.63
D
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.38
T
MetaSVM
Uncertain
0.22
D
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
0.96
D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.19
T
Polyphen
0.82
P
Vest4
0.37
MutPred
0.23
Loss of helix (P = 0.0558);
MVP
0.83
ClinPred
0.88
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.41
gMVP
0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144787962; hg19: chr22-41574622; API