rs3818120

chr22-41127766-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001429.4(EP300):c.1168+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,613,940 control chromosomes in the GnomAD database, including 1,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (429 hom., cov: 31)
  • Exomes 𝑓: 0.0092 (1006 hom.)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0130

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-41127766-G-A is Benign according to our data. Variant chr22-41127766-G-A is described in ClinVar as [Benign]. Clinvar id is 258094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4	c.1168+18G>A		intron_variant		ENST00000263253.9
EP300	NM_001362843.2	c.1168+18G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9	c.1168+18G>A		intron_variant		1	NM_001429.4	P2

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6240 AN: 152198 Hom.: 428 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000852

Gnomad OTH AF: 0.0339

GnomAD3 exomes AF: 0.0265 AC: 6625 AN: 249600 Hom.: 602 AF XY: 0.0228 AC XY: 3087 AN XY: 135116

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.00622

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.231

Gnomad SAS exome AF: 0.00653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000473

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.00923 AC: 13497 AN: 1461622 Hom.: 1006 Cov.: 31 AF XY: 0.00885 AC XY: 6437 AN XY: 727084

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.00756

Gnomad4 ASJ exome AF: 0.000497

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.00757

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000331

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0410 AC: 6247 AN: 152318 Hom.: 429 Cov.: 31 AF XY: 0.0406 AC XY: 3023 AN XY: 74488

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000852

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0181 Hom.: 20

Bravo AF: 0.0452

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.55
Dann	Benign	0.28
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: rs3818120; hg19: chr22-41523770; COSMIC: COSV54333412; COSMIC: COSV54333412;