rs11912899
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001429.4(EP300):c.6210G>A(p.Val2070=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,614,154 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )
Consequence
EP300
NM_001429.4 synonymous
NM_001429.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.08
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 22-41177921-G-A is Benign according to our data. Variant chr22-41177921-G-A is described in ClinVar as [Benign]. Clinvar id is 538875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.08 with no splicing effect.
BS2
?
High AC in GnomAd4 at 198 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.6210G>A | p.Val2070= | synonymous_variant | 31/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.6132G>A | p.Val2044= | synonymous_variant | 30/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.6210G>A | p.Val2070= | synonymous_variant | 31/31 | 1 | NM_001429.4 | P2 | |
ENST00000415054.1 | n.82+5142C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
EP300-AS1 | ENST00000420537.1 | n.224-3097C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
EP300 | ENST00000674155.1 | c.6132G>A | p.Val2044= | synonymous_variant | 30/30 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00130 AC: 198AN: 152142Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000362 AC: 91AN: 251414Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135882
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GnomAD4 exome AF: 0.000118 AC: 172AN: 1461894Hom.: 1 Cov.: 31 AF XY: 0.000100 AC XY: 73AN XY: 727248
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GnomAD4 genome ? AF: 0.00130 AC: 198AN: 152260Hom.: 2 Cov.: 32 AF XY: 0.00116 AC XY: 86AN XY: 74448
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | EP300: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 28, 2018 | - - |
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
EP300-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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