rs1210404526

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_001429.4(EP300):c.6001C>G(p.Pro2001Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2001S) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.891

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]

EP300 links:

(HGNC:):

links:

EP300-AS1 (HGNC:50504): (EP300 antisense RNA 1)

EP300-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr22-41177712-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 438594.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.

BP4

Computational evidence support a benign effect (MetaRNN=0.30110508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4 linkuse as main transcript	c.6001C>G	p.Pro2001Ala	missense_variant	31/31	ENST00000263253.9
EP300	NM_001362843.2 linkuse as main transcript	c.5923C>G	p.Pro1975Ala	missense_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EP300	ENST00000263253.9 linkuse as main transcript	c.6001C>G	p.Pro2001Ala	missense_variant	31/31	1	NM_001429.4	P2
	ENST00000415054.1 linkuse as main transcript	n.82+5351G>C		intron_variant, non_coding_transcript_variant		3
EP300-AS1	ENST00000420537.1 linkuse as main transcript	n.224-2888G>C		intron_variant, non_coding_transcript_variant		3
EP300	ENST00000674155.1 linkuse as main transcript	c.5923C>G	p.Pro1975Ala	missense_variant	30/30			A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251038

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135694

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727072

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000470

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.0070

BayesDel_noAF

Benign

-0.25

Cadd

Benign

Dann

Benign

0.91

DEOGEN2

Uncertain

0.69

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

M_CAP

Benign

0.048

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.99

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.27

Sift

Uncertain

0.024

Sift4G

Benign

0.10

Polyphen

0.089

Vest4

0.42

MutPred

0.52

Loss of glycosylation at P2001 (P = 0.0671);

MVP

0.80

ClinPred

0.24

GERP RS

4.2

Varity_R

0.19

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over