rs1555911316
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM4PP3PP5_Moderate
The NM_001429.4(EP300):c.4371_4376del(p.Ile1457_Lys1459delinsMet) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
EP300
NM_001429.4 inframe_deletion
NM_001429.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.22
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a binding_site (size 0) in uniprot entity EP300_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_001429.4.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 22-41170489-TACCCAA-T is Pathogenic according to our data. Variant chr22-41170489-TACCCAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 438290.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.4371_4376del | p.Ile1457_Lys1459delinsMet | inframe_deletion | 27/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.4293_4298del | p.Ile1431_Lys1433delinsMet | inframe_deletion | 26/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.4371_4376del | p.Ile1457_Lys1459delinsMet | inframe_deletion | 27/31 | 1 | NM_001429.4 | P2 | |
ENST00000415054.1 | n.83-914_83-909del | intron_variant, non_coding_transcript_variant | 3 | ||||||
EP300 | ENST00000674155.1 | c.4293_4298del | p.Ile1431_Lys1433delinsMet | inframe_deletion | 26/30 | A2 | |||
EP300 | ENST00000703544.1 | c.*2291_*2296del | 3_prime_UTR_variant, NMD_transcript_variant | 26/30 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals | Sep 15, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2022 | Reported in a patient in published literature with features of Rubinstein-Taybi syndrome (Fergelot et al., 2016); In-frame deletion of 3 amino acids and insertion of 1 incorrect amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27648933) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at