Variant rs61120041 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001429.4(EP300):c.730-18_730-9del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0122 in 1,611,928 control chromosomes in the GnomAD database, including 1,413 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 419 hom., cov: 31)

Exomes 𝑓: 0.0091 ( 994 hom. )

Consequence

EP300
NM_001429.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 4.05

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 22-41125844-CTTTTGTTTCT-C is Benign according to our data. Variant chr22-41125844-CTTTTGTTTCT-C is described in ClinVar as [Benign]. Clinvar id is 93745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4 linkuse as main transcript	c.730-18_730-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263253.9
EP300	NM_001362843.2 linkuse as main transcript	c.730-18_730-9del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9 linkuse as main transcript	c.730-18_730-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001429.4	P2

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

6230

AN:

152040

Hom.:

418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0261

AC:

6543

AN:

250674

Hom.:

565

AF XY:

0.0225

AC XY:

3046

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.00616

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.00642

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.00915

AC:

13350

AN:

1459770

Hom.:

994

AF XY:

0.00878

AC XY:

6377

AN XY:

726298

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.00751

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.00750

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.0195

GnomAD4 genome

AF:

0.0410

AC:

6237

AN:

152158

Hom.:

419

Cov.:

AF XY:

0.0406

AC XY:

3019

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.0337

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0451

Asia WGS

AF:

0.0820

AC:

286

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 01, 2013	- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Rubinstein-Taybi syndrome due to CREBBP mutations

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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