Variant chr22-41173605-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001429.4(EP300):c.4618-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,612,728 control chromosomes in the GnomAD database, including 89,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6240 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83759 hom. )

Consequence

EP300
NM_001429.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.374

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 22-41173605-C-T is Benign according to our data. Variant chr22-41173605-C-T is described in ClinVar as [Benign]. Clinvar id is 93742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41173605-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP300	NM_001429.4 linkuse as main transcript	c.4618-18C>T		intron_variant		ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2 linkuse as main transcript	c.4540-18C>T		intron_variant			NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
EP300	ENST00000263253.9 linkuse as main transcript	c.4618-18C>T	intron_variant	1	NM_001429.4	ENSP00000263253	P2
	ENST00000415054.1 linkuse as main transcript	n.83-4024G>A	intron_variant, non_coding_transcript_variant	3
EP300	ENST00000674155.1 linkuse as main transcript	c.4540-18C>T	intron_variant			ENSP00000501078	A2
EP300	ENST00000703544.1 linkuse as main transcript	c.*2538-18C>T	intron_variant, NMD_transcript_variant			ENSP00000515365

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40153

AN:

151988

Hom.:

6244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0953

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.303

AC:

75857

AN:

250128

Hom.:

12652

AF XY:

0.309

AC XY:

41853

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.466

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.332

AC:

484654

AN:

1460622

Hom.:

83759

Cov.:

AF XY:

0.332

AC XY:

240873

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.0874

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.295

Gnomad4 EAS exome

AF:

0.547

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.264

AC:

40149

AN:

152106

Hom.:

6240

Cov.:

AF XY:

0.263

AC XY:

19568

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0954

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.303

Gnomad4 EAS

AF:

0.492

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.291

Hom.:

1829

Bravo

AF:

0.257

Asia WGS

AF:

0.379

AC:

1316

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 11, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.81

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