rs3818120
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001429.4(EP300):c.1168+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,613,940 control chromosomes in the GnomAD database, including 1,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.041 ( 429 hom., cov: 31)
Exomes 𝑓: 0.0092 ( 1006 hom. )
Consequence
EP300
NM_001429.4 intron
NM_001429.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0130
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 22-41127766-G-A is Benign according to our data. Variant chr22-41127766-G-A is described in ClinVar as [Benign]. Clinvar id is 258094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.1168+18G>A | intron_variant | ENST00000263253.9 | |||
EP300 | NM_001362843.2 | c.1168+18G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.1168+18G>A | intron_variant | 1 | NM_001429.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0410 AC: 6240AN: 152198Hom.: 428 Cov.: 31
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GnomAD3 exomes AF: 0.0265 AC: 6625AN: 249600Hom.: 602 AF XY: 0.0228 AC XY: 3087AN XY: 135116
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GnomAD4 exome AF: 0.00923 AC: 13497AN: 1461622Hom.: 1006 Cov.: 31 AF XY: 0.00885 AC XY: 6437AN XY: 727084
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GnomAD4 genome ? AF: 0.0410 AC: 6247AN: 152318Hom.: 429 Cov.: 31 AF XY: 0.0406 AC XY: 3023AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 27, 2018 | - - |
Computational scores
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Name
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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