22-41093056-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_001429.4(EP300):ā€‹c.52C>Gā€‹(p.Leu18Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

13
6

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.81
Variant links:
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 -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.40559486).
BP6
Variant 22-41093056-C-G is Benign according to our data. Variant chr22-41093056-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3661913.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EP300NM_001429.4 linkc.52C>G p.Leu18Val missense_variant Exon 1 of 31 ENST00000263253.9 NP_001420.2 Q09472Q7Z6C1
EP300NM_001362843.2 linkc.52C>G p.Leu18Val missense_variant Exon 1 of 30 NP_001349772.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EP300ENST00000263253.9 linkc.52C>G p.Leu18Val missense_variant Exon 1 of 31 1 NM_001429.4 ENSP00000263253.7 Q09472
EP300ENST00000674155.1 linkc.52C>G p.Leu18Val missense_variant Exon 1 of 30 ENSP00000501078.1 A0A669KB12
EP300ENST00000703544.1 linkn.52C>G non_coding_transcript_exon_variant Exon 1 of 30 ENSP00000515365.1 A0A994J6T4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250958
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461824
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Jan 07, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.084
D
MetaRNN
Benign
0.41
T
MetaSVM
Uncertain
0.60
D
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.7
N
REVEL
Uncertain
0.38
Sift
Uncertain
0.0020
D
Sift4G
Benign
0.061
T
Polyphen
0.99
D
Vest4
0.43
MutPred
0.15
Loss of loop (P = 0.0603);
MVP
0.83
ClinPred
0.97
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.52
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777392825; hg19: chr22-41489060; API