rs9611502

Variant names:

• chr22-41135232-C-T
• rs9611502
• NM_001429.4:c.1529-581C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001429.4(EP300):​c.1529-581C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 152,268 control chromosomes in the GnomAD database, including 89 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 0.026 (89 hom., cov: 33)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.1529-581C>T		intron_variant	Intron 6 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.1529-581C>T		intron_variant	Intron 6 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.1529-581C>T		intron_variant	Intron 6 of 30	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4021 AN: 152150 Hom.: 90 Cov.: 33

Gnomad AFR AF: 0.00623

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0264 AC: 4020 AN: 152268 Hom.: 89 Cov.: 33 AF XY: 0.0270 AC XY: 2013 AN XY: 74446

Gnomad4 AFR AF: 0.00621

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0841

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0356 Hom.: 161

Bravo AF: 0.0231

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs9611502; hg19: chr22-41531236;