rs17002316

Variant names:

• chr22-41149746-T-C
• rs17002316
• NM_001429.4:c.2380-15T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001429.4(EP300):​c.2380-15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,804 control chromosomes in the GnomAD database, including 1,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (433 hom., cov: 31)
  • Exomes 𝑓: 0.0092 (1004 hom.)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.152
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-41149746-T-C is Benign according to our data. Variant chr22-41149746-T-C is described in ClinVar as Benign. ClinVar VariationId is 158559.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 rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.2380-15T>C		intron_variant	Intron 13 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.2302-15T>C		intron_variant	Intron 12 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.2380-15T>C		intron_variant	Intron 13 of 30	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6310 AN: 152104 Hom.: 432 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0336

GnomAD2 exomes AF: 0.0264 AC: 6633 AN: 250922 AF XY: 0.0227

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.00625

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.00923 AC: 13492 AN: 1461582 Hom.: 1004 Cov.: 32 AF XY: 0.00885 AC XY: 6436 AN XY: 727116

African (AFR) AF: 0.117 AC: 3907 AN: 33466

American (AMR) AF: 0.00760 AC: 340 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26132

East Asian (EAS) AF: 0.177 AC: 7031 AN: 39698

South Asian (SAS) AF: 0.00757 AC: 653 AN: 86244

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53344

Middle Eastern (MID) AF: 0.00728 AC: 42 AN: 5768

European-Non Finnish (NFE) AF: 0.000329 AC: 366 AN: 1111820

Other (OTH) AF: 0.0189 AC: 1139 AN: 60392

GnomAD4 genome AF: 0.0415 AC: 6317 AN: 152222 Hom.: 433 Cov.: 31 AF XY: 0.0411 AC XY: 3063 AN XY: 74436

African (AFR) AF: 0.116 AC: 4827 AN: 41492

American (AMR) AF: 0.0145 AC: 221 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1070 AN: 5182

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68028

Other (OTH) AF: 0.0332 AC: 70 AN: 2106

Alfa AF: 0.0170 Hom.: 44

Bravo AF: 0.0457

Asia WGS AF: 0.0810 AC: 282 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

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jul 27, 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 02, 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	-0.83
CADD	Benign	6.2
DANN	Benign	0.62
PhyloP100		-0.15
Mutation Taster		=100/0	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: rs17002316; hg19: chr22-41545750; COSMIC: COSV54333432; COSMIC: COSV54333432;