rs1555910602
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_001429.4(EP300):c.3734_3736del(p.Val1245del) variant causes a inframe deletion, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
EP300
NM_001429.4 inframe_deletion, splice_region
NM_001429.4 inframe_deletion, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 10.0
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 6 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 4 uncertain in NM_001429.4
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_001429.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 22-41164054-TTTG-T is Pathogenic according to our data. Variant chr22-41164054-TTTG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438292.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.3734_3736del | p.Val1245del | inframe_deletion, splice_region_variant | 22/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.3656_3658del | p.Val1219del | inframe_deletion, splice_region_variant | 21/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.3734_3736del | p.Val1245del | inframe_deletion, splice_region_variant | 22/31 | 1 | NM_001429.4 | P2 | |
EP300 | ENST00000674155.1 | c.3656_3658del | p.Val1219del | inframe_deletion, splice_region_variant | 21/30 | A2 | |||
EP300 | ENST00000635584.1 | n.59_61del | splice_region_variant, non_coding_transcript_exon_variant | 2/6 | 4 | ||||
EP300 | ENST00000703544.1 | c.*1654_*1656del | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 21/30 |
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: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
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 | Feb 12, 2016 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at