rs35508493

Variant names:

• chr22-41178965-TGTA-T
• rs35508493
• NM_001429.4:c.*13_*15delGTA

Your query was ambiguous. Multiple possible variants found:

• chr22-41178965-TGTA-T
• chr22-41178965-TGTA-TGTAGTA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001429.4(EP300):​c.*13_*15delGTA 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
• Publications: 10 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-AS1 (HGNC:50504): (EP300 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 158555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.*13_*15delGTA		3_prime_UTR_variant	Exon 31 of 31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.*13_*15delGTA		3_prime_UTR_variant	Exon 30 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.*13_*15delGTA		3_prime_UTR_variant	Exon 31 of 31	1	NM_001429.4	ENSP00000263253.7

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

GnomAD2 exomes AF: 0.311 AC: 77213 AN: 247962 AF XY: 0.308

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 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

African (AFR) AF: 0.111 AC: 3700 AN: 33450

American (AMR) AF: 0.594 AC: 26381 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8463 AN: 26096

East Asian (EAS) AF: 0.0414 AC: 1643 AN: 39698

South Asian (SAS) AF: 0.369 AC: 31799 AN: 86128

European-Finnish (FIN) AF: 0.312 AC: 16567 AN: 53062

Middle Eastern (MID) AF: 0.287 AC: 1656 AN: 5764

European-Non Finnish (NFE) AF: 0.275 AC: 305226 AN: 1111336

Other (OTH) AF: 0.278 AC: 16767 AN: 60352

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

African (AFR) AF: 0.121 AC: 5007 AN: 41504

American (AMR) AF: 0.446 AC: 6801 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3468

East Asian (EAS) AF: 0.0575 AC: 298 AN: 5182

South Asian (SAS) AF: 0.368 AC: 1773 AN: 4822

European-Finnish (FIN) AF: 0.312 AC: 3293 AN: 10550

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18021 AN: 67952

Other (OTH) AF: 0.264 AC: 559 AN: 2116

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 10, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Dec 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8
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: rs35508493; hg19: chr22-41574969; COSMIC: COSV54333767; COSMIC: COSV54333767;