22-41093033-C-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2
The NM_001429.4(EP300):āc.29C>Gā(p.Pro10Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
EP300
NM_001429.4 missense
NM_001429.4 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 6.81
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 -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.844
BP6
Variant 22-41093033-C-G is Benign according to our data. Variant chr22-41093033-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3038262.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAdExome4 at 39 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.29C>G | p.Pro10Arg | missense_variant | 1/31 | ENST00000263253.9 | NP_001420.2 | |
EP300 | NM_001362843.2 | c.29C>G | p.Pro10Arg | missense_variant | 1/30 | NP_001349772.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.29C>G | p.Pro10Arg | missense_variant | 1/31 | 1 | NM_001429.4 | ENSP00000263253.7 | ||
EP300 | ENST00000674155.1 | c.29C>G | p.Pro10Arg | missense_variant | 1/30 | ENSP00000501078.1 | ||||
EP300 | ENST00000703544.1 | n.29C>G | non_coding_transcript_exon_variant | 1/30 | ENSP00000515365.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251076Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135834
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727214
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
EP300-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 04, 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of glycosylation at P10 (P = 0.0143);
MVP
ClinPred
D
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gMVP
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at