rs17002284

Variant names:

• chr22-41100842-A-G
• rs17002284
• NM_001429.4:c.94+7744A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-41100842-A-G
• chr22-41100842-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001429.4(EP300):​c.94+7744A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,840 control chromosomes in the GnomAD database, including 6,368 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6368 hom., cov: 30)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• 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 Gene-Disease associations (from GenCC):

• Rubinstein-Taybi syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.94+7744A>G		intron_variant	Intron 1 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.94+7744A>G		intron_variant	Intron 1 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.94+7744A>G		intron_variant	Intron 1 of 30	1	NM_001429.4	ENSP00000263253.7
EP300	ENST00000715703.1	c.94+7744A>G		intron_variant	Intron 1 of 30			ENSP00000520505.1
EP300	ENST00000674155.1	c.94+7744A>G		intron_variant	Intron 1 of 29			ENSP00000501078.1
EP300	ENST00000703544.1	n.94+7744A>G		intron_variant	Intron 1 of 29			ENSP00000515365.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39656 AN: 151722 Hom.: 6376 Cov.: 30

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39634 AN: 151840 Hom.: 6368 Cov.: 30 AF XY: 0.261 AC XY: 19347 AN XY: 74198

African (AFR) AF: 0.0704 AC: 2916 AN: 41446

American (AMR) AF: 0.285 AC: 4333 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2785 AN: 5152

South Asian (SAS) AF: 0.309 AC: 1487 AN: 4814

European-Finnish (FIN) AF: 0.276 AC: 2913 AN: 10536

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23174 AN: 67910

Other (OTH) AF: 0.300 AC: 629 AN: 2098

Alfa AF: 0.269 Hom.: 804

Bravo AF: 0.254

Asia WGS AF: 0.412 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.97
DANN	Benign	0.69
PhyloP100		-0.60
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: rs17002284; hg19: chr22-41496846;