rs17433014

Positions:

• chr22-41103818-G-A
• chr22-41103818-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001429.4(EP300):​c.94+10720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 152,278 control chromosomes in the GnomAD database, including 110 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 0.030 (110 hom., cov: 32)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.898

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=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0301 (4590/152278) while in subpopulation NFE AF= 0.039 (2651/68026). AF 95% confidence interval is 0.0377. There are 110 homozygotes in gnomad4. There are 2314 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4590 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4	c.94+10720G>A		intron_variant		ENST00000263253.9
EP300	NM_001362843.2	c.94+10720G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9	c.94+10720G>A		intron_variant		1	NM_001429.4	P2
EP300	ENST00000674155.1	c.94+10720G>A		intron_variant				A2
EP300	ENST00000703544.1	c.94+10720G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4594 AN: 152160 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.00671

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0623

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0301 AC: 4590 AN: 152278 Hom.: 110 Cov.: 32 AF XY: 0.0311 AC XY: 2314 AN XY: 74454

Gnomad4 AFR AF: 0.00669

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.0623

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0200 Hom.: 12

Bravo AF: 0.0257

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17433014; hg19: chr22-41499822;