rs587778257

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000263253.9(EP300):​c.5552C>T​(p.Thr1851Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EP300
ENST00000263253.9 missense

Scores

1
11
7

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 4.38
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EP300NM_001429.4 linkuse as main transcriptc.5552C>T p.Thr1851Ile missense_variant 31/31 ENST00000263253.9 NP_001420.2
EP300NM_001362843.2 linkuse as main transcriptc.5474C>T p.Thr1825Ile missense_variant 30/30 NP_001349772.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EP300ENST00000263253.9 linkuse as main transcriptc.5552C>T p.Thr1851Ile missense_variant 31/311 NM_001429.4 ENSP00000263253 P2
ENST00000415054.1 linkuse as main transcriptn.82+5800G>A intron_variant, non_coding_transcript_variant 3
EP300-AS1ENST00000420537.1 linkuse as main transcriptn.224-2439G>A intron_variant, non_coding_transcript_variant 3
EP300ENST00000674155.1 linkuse as main transcriptc.5474C>T p.Thr1825Ile missense_variant 30/30 ENSP00000501078 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727238
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Pathogenic
0.81
D
Eigen
Benign
0.18
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.86
D
M_CAP
Uncertain
0.095
D
MetaRNN
Uncertain
0.71
D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
0.89
N
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.23
Sift
Uncertain
0.0050
D
Sift4G
Benign
0.14
T
Polyphen
0.84
P
Vest4
0.62
MutPred
0.17
Loss of glycosylation at T1851 (P = 0.005);
MVP
0.84
ClinPred
0.90
D
GERP RS
5.5
Varity_R
0.17
gMVP
0.13

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: rs587778257; hg19: chr22-41573267; API