rs875989807
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_001429.4(EP300):c.6574_6585delCAGCAGCAACAG(p.Gln2192_Gln2195del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000147 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
EP300
NM_001429.4 conservative_inframe_deletion
NM_001429.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.67
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_benign. Variant got -2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001429.4.
BS2
High AC in GnomAd4 at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.6574_6585delCAGCAGCAACAG | p.Gln2192_Gln2195del | conservative_inframe_deletion | 31/31 | ENST00000263253.9 | NP_001420.2 | |
EP300 | NM_001362843.2 | c.6496_6507delCAGCAGCAACAG | p.Gln2166_Gln2169del | conservative_inframe_deletion | 30/30 | NP_001349772.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.6574_6585delCAGCAGCAACAG | p.Gln2192_Gln2195del | conservative_inframe_deletion | 31/31 | 1 | NM_001429.4 | ENSP00000263253.7 | ||
EP300 | ENST00000674155.1 | c.6496_6507delCAGCAGCAACAG | p.Gln2166_Gln2169del | conservative_inframe_deletion | 30/30 | ENSP00000501078.1 | ||||
ENSG00000232754 | ENST00000415054.1 | n.82+4774_82+4785delTGCTGCTGTTGC | intron_variant | 3 | ||||||
EP300-AS1 | ENST00000420537.1 | n.224-3465_224-3454delTGCTGCTGTTGC | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152018Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000271 AC: 68AN: 251352Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135862
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GnomAD4 exome AF: 0.000138 AC: 202AN: 1461882Hom.: 0 AF XY: 0.000144 AC XY: 105AN XY: 727244
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GnomAD4 genome AF: 0.000237 AC: 36AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74252
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ClinVar
Significance: Likely benign
Submissions summary: Pathogenic:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Pathogenic:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | - - |
Likely pathogenic, flagged submission | literature only | Center for Human Genetics, University of Leuven | Jan 01, 2015 | - - |
EP300-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 08, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | EP300: BS2 - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at