NM_001429.4:c.5061+9C>T

Variant names:

• chr22-41176537-C-T
• rs73176628
• NM_001429.4:c.5061+9C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001429.4(EP300):​c.5061+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 1,613,432 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (57 hom., cov: 32)
  • Exomes 𝑓: 0.025 (593 hom.)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.656
• Publications: 5 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=-0.88).
• BP6: Variant 22-41176537-C-T is Benign according to our data. Variant chr22-41176537-C-T is described in ClinVar as Benign. ClinVar VariationId is 158566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0208 (3171/152180) while in subpopulation SAS AF = 0.0338 (163/4818). AF 95% confidence interval is 0.0296. There are 57 homozygotes in GnomAd4. There are 1670 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3171 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001429.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	NM_001429.4	MANE Select	c.5061+9C>T		intron	N/A	NP_001420.2
	EP300	NM_001362843.2		c.4983+9C>T		intron	N/A	NP_001349772.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	ENST00000263253.9	TSL:1 MANE Select	c.5061+9C>T		intron	N/A	ENSP00000263253.7
	EP300	ENST00000715703.1		c.5061+9C>T		intron	N/A	ENSP00000520505.1
	EP300	ENST00000674155.1		c.4983+9C>T		intron	N/A	ENSP00000501078.1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3169 AN: 152062 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.0258 AC: 6445 AN: 249560 AF XY: 0.0274

Gnomad AFR exome AF: 0.00371

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.0616

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0588

Gnomad NFE exome AF: 0.0253

Gnomad OTH exome AF: 0.0302

GnomAD4 exome AF: 0.0251 AC: 36731 AN: 1461252 Hom.: 593 Cov.: 31 AF XY: 0.0259 AC XY: 18819 AN XY: 726920

African (AFR) AF: 0.00436 AC: 146 AN: 33464

American (AMR) AF: 0.0108 AC: 482 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 1564 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0375 AC: 3234 AN: 86220

European-Finnish (FIN) AF: 0.0549 AC: 2934 AN: 53396

Middle Eastern (MID) AF: 0.0534 AC: 288 AN: 5390

European-Non Finnish (NFE) AF: 0.0238 AC: 26475 AN: 1111922

Other (OTH) AF: 0.0266 AC: 1603 AN: 60322

GnomAD4 genome AF: 0.0208 AC: 3171 AN: 152180 Hom.: 57 Cov.: 32 AF XY: 0.0224 AC XY: 1670 AN XY: 74402

African (AFR) AF: 0.00484 AC: 201 AN: 41534

American (AMR) AF: 0.0179 AC: 274 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4818

European-Finnish (FIN) AF: 0.0560 AC: 593 AN: 10586

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1637 AN: 68012

Other (OTH) AF: 0.0227 AC: 48 AN: 2110

Alfa AF: 0.0243 Hom.: 81

Bravo AF: 0.0178

Asia WGS AF: 0.0160 AC: 56 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

Sep 16, 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.66
DANN	Benign	0.77
PhyloP100		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs73176628; hg19: chr22-41572541; COSMIC: COSV99610297;