rs2294976

Variant names:

• chr22-41168704-C-A
• rs2294976
• NM_001429.4:c.4026-17C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-41168704-C-A
• chr22-41168704-C-G
• chr22-41168704-C-T

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.4026-17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,614,098 control chromosomes in the GnomAD database, including 7,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (556 hom., cov: 32)
  • Exomes 𝑓: 0.090 (6501 hom.)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.00700
• Publications: 16 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=-0.79).
• BP6: Variant 22-41168704-C-A is Benign according to our data. Variant chr22-41168704-C-A is described in ClinVar as Benign. ClinVar VariationId is 93740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	NM_001429.4	MANE Select	c.4026-17C>A		intron	N/A	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.3948-17C>A		intron	N/A	NP_001349772.1	A0A669KB12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	ENST00000263253.9	TSL:1 MANE Select	c.4026-17C>A		intron	N/A	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.4056-17C>A		intron	N/A	ENSP00000586141.1
	EP300	ENST00000715703.1		c.4026-17C>A		intron	N/A	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11182 AN: 152158 Hom.: 547 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0879

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.0866

GnomAD2 exomes AF: 0.0888 AC: 22314 AN: 251400 AF XY: 0.0921

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.0466

Gnomad ASJ exome AF: 0.0771

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.0880

Gnomad NFE exome AF: 0.0919

Gnomad OTH exome AF: 0.0913

GnomAD4 exome AF: 0.0897 AC: 131155 AN: 1461822 Hom.: 6501 Cov.: 33 AF XY: 0.0909 AC XY: 66122 AN XY: 727210

African (AFR) AF: 0.0260 AC: 869 AN: 33480

American (AMR) AF: 0.0496 AC: 2217 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0794 AC: 2075 AN: 26134

East Asian (EAS) AF: 0.175 AC: 6936 AN: 39696

South Asian (SAS) AF: 0.110 AC: 9521 AN: 86256

European-Finnish (FIN) AF: 0.0886 AC: 4733 AN: 53420

Middle Eastern (MID) AF: 0.118 AC: 683 AN: 5768

European-Non Finnish (NFE) AF: 0.0885 AC: 98452 AN: 1111950

Other (OTH) AF: 0.0939 AC: 5669 AN: 60394

GnomAD4 genome AF: 0.0736 AC: 11204 AN: 152276 Hom.: 556 Cov.: 32 AF XY: 0.0728 AC XY: 5419 AN XY: 74456

African (AFR) AF: 0.0280 AC: 1162 AN: 41566

American (AMR) AF: 0.0585 AC: 894 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.169 AC: 875 AN: 5182

South Asian (SAS) AF: 0.108 AC: 521 AN: 4830

European-Finnish (FIN) AF: 0.0879 AC: 931 AN: 10596

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0925 AC: 6294 AN: 68022

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.0862 Hom.: 1195

Bravo AF: 0.0690

Asia WGS AF: 0.182 AC: 629 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.33
PhyloP100		0.0070
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2294976;

hg19: chr22-41564708;

COSMIC: COSV54326727;

COSMIC: COSV54326727;