rs147244947
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001429.4(EP300):c.678C>G(p.Gly226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,220 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 29 hom. )
Consequence
EP300
NM_001429.4 synonymous
NM_001429.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.116
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 22-41117770-C-G is Benign according to our data. Variant chr22-41117770-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 341781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.116 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00194 (296/152344) while in subpopulation EAS AF= 0.0191 (99/5194). AF 95% confidence interval is 0.016. There are 2 homozygotes in gnomad4. There are 167 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 294 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.678C>G | p.Gly226= | synonymous_variant | 2/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.678C>G | p.Gly226= | synonymous_variant | 2/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.678C>G | p.Gly226= | synonymous_variant | 2/31 | 1 | NM_001429.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00193 AC: 294AN: 152226Hom.: 2 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
294
AN:
152226
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00258 AC: 648AN: 251276Hom.: 3 AF XY: 0.00262 AC XY: 356AN XY: 135848
GnomAD3 exomes
AF:
AC:
648
AN:
251276
Hom.:
AF XY:
AC XY:
356
AN XY:
135848
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00191 AC: 2787AN: 1461876Hom.: 29 Cov.: 32 AF XY: 0.00209 AC XY: 1519AN XY: 727238
GnomAD4 exome
AF:
AC:
2787
AN:
1461876
Hom.:
Cov.:
32
AF XY:
AC XY:
1519
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00194 AC: 296AN: 152344Hom.: 2 Cov.: 33 AF XY: 0.00224 AC XY: 167AN XY: 74512
GnomAD4 genome
?
AF:
AC:
296
AN:
152344
Hom.:
Cov.:
33
AF XY:
AC XY:
167
AN XY:
74512
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
27
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely 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 | Oct 01, 2023 | EP300: BP4, BP7, BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2021 | - - |
EP300-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 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). - |
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at