Variant 22-41093069-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001429.4(EP300):c.65C>T(p.Ala22Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

EP300
NM_001429.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4 link	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 31	ENST00000263253.9	NP_001420.2	Q09472Q7Z6C1
EP300	NM_001362843.2 link	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EP300	ENST00000263253.9 link	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 31	1	NM_001429.4	ENSP00000263253.7	Q09472
EP300	ENST00000674155.1 link	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 30			ENSP00000501078.1	A0A669KB12
EP300	ENST00000703544.1 link	n.65C>T		non_coding_transcript_exon_variant	Exon 1 of 30			ENSP00000515365.1	A0A994J6T4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250664

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135638

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000369

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EP300-related disorder

Uncertain:1

Jun 05, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The EP300 c.65C>T variant is predicted to result in the amino acid substitution p.Ala22Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.54

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.38

Sift

Uncertain

0.0040

Sift4G

Benign

0.24

Polyphen

1.0

Vest4

0.52

MutPred

0.14

Gain of sheet (P = 0.0477);

MVP

0.82

ClinPred

0.95

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.35

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over