rs35508493

chr22-41178965-TGTA-Tchr22-41178965-TGTA-TGTAGTA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001429.4(EP300):c.*13_*15del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.279 in 1,612,364 control chromosomes in the GnomAD database, including 68,745 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5469 hom., cov: 24)
  • Exomes 𝑓: 0.28 (63276 hom.)
• Consequence: EP300 NM_001429.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.78

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]

(HGNC:):

EP300-AS1 (HGNC:50504): (EP300 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 22-41178965-TGTA-T is Benign according to our data. Variant chr22-41178965-TGTA-T is described in ClinVar as [Benign]. Clinvar id is 158555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41178965-TGTA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4	c.*13_*15del		3_prime_UTR_variant	31/31	ENST00000263253.9
EP300	NM_001362843.2	c.*13_*15del		3_prime_UTR_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9	c.*13_*15del		3_prime_UTR_variant	31/31	1	NM_001429.4	P2
	ENST00000415054.1	n.82+4095_82+4097del		intron_variant, non_coding_transcript_variant		3
EP300-AS1	ENST00000420537.1	n.224-4144_224-4142del		intron_variant, non_coding_transcript_variant		3
EP300	ENST00000674155.1	c.*13_*15del		3_prime_UTR_variant	30/30			A2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37294 AN: 151940 Hom.: 5458 Cov.: 24

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.267

GnomAD3 exomes AF: 0.311 AC: 77213 AN: 247962 Hom.: 14938 AF XY: 0.308 AC XY: 41454 AN XY: 134776

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.615

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.0617

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.282 AC: 412202 AN: 1460306 Hom.: 63276 AF XY: 0.284 AC XY: 206545 AN XY: 726424

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.594

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.0414

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.245 AC: 37316 AN: 152058 Hom.: 5469 Cov.: 24 AF XY: 0.254 AC XY: 18902 AN XY: 74332

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.264

Alfa AF: 0.250 Hom.: 604

Bravo AF: 0.252

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 10, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs35508493; hg19: chr22-41574969;