rs2076578

Variant names:

• chr22-41173605-C-T
• rs2076578
• NM_001429.4:c.4618-18C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.374
• Publications: 19 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 93742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.4618-18C>T		intron_variant	Intron 28 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.4540-18C>T		intron_variant	Intron 27 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.4618-18C>T		intron_variant	Intron 28 of 30	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40153 AN: 151988 Hom.: 6244 Cov.: 32

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

GnomAD2 exomes AF: 0.303 AC: 75857 AN: 250128 AF XY: 0.309

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 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.: 34 AF XY: 0.332 AC XY: 240873 AN XY: 726574

African (AFR) AF: 0.0874 AC: 2926 AN: 33468

American (AMR) AF: 0.206 AC: 9186 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 7709 AN: 26112

East Asian (EAS) AF: 0.547 AC: 21713 AN: 39684

South Asian (SAS) AF: 0.290 AC: 24976 AN: 86150

European-Finnish (FIN) AF: 0.290 AC: 15462 AN: 53378

Middle Eastern (MID) AF: 0.281 AC: 1623 AN: 5768

European-Non Finnish (NFE) AF: 0.344 AC: 381953 AN: 1111078

Other (OTH) AF: 0.317 AC: 19106 AN: 60344

GnomAD4 genome AF: 0.264 AC: 40149 AN: 152106 Hom.: 6240 Cov.: 32 AF XY: 0.263 AC XY: 19568 AN XY: 74358

African (AFR) AF: 0.0954 AC: 3962 AN: 41518

American (AMR) AF: 0.265 AC: 4048 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3466

East Asian (EAS) AF: 0.492 AC: 2544 AN: 5168

South Asian (SAS) AF: 0.302 AC: 1456 AN: 4818

European-Finnish (FIN) AF: 0.275 AC: 2905 AN: 10570

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23210 AN: 67968

Other (OTH) AF: 0.293 AC: 619 AN: 2112

Alfa AF: 0.287 Hom.: 1835

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

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 11, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.37
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076578; hg19: chr22-41569609; COSMIC: COSV54325089; COSMIC: COSV54325089;