22-41170591-C-T

Variant names:

• chr22-41170591-C-T
• rs6002271
• NM_001429.4:c.4452+20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001429.4(EP300):​c.4452+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,609,458 control chromosomes in the GnomAD database, including 71,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5529 hom., cov: 31)
  • Exomes 𝑓: 0.29 (66253 hom.)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.157
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-41170591-C-T is Benign according to our data. Variant chr22-41170591-C-T is described in ClinVar as Benign. ClinVar VariationId is 93741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001429.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	NM_001429.4	MANE Select	c.4452+20C>T		intron	N/A	NP_001420.2
	EP300	NM_001362843.2		c.4374+20C>T		intron	N/A	NP_001349772.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	ENST00000263253.9	TSL:1 MANE Select	c.4452+20C>T		intron	N/A	ENSP00000263253.7
	EP300	ENST00000715703.1		c.4452+20C>T		intron	N/A	ENSP00000520505.1
	EP300	ENST00000674155.1		c.4374+20C>T		intron	N/A	ENSP00000501078.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37605 AN: 151180 Hom.: 5518 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.272

GnomAD2 exomes AF: 0.314 AC: 78725 AN: 250960 AF XY: 0.311

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.0614

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.290 AC: 422738 AN: 1458168 Hom.: 66253 Cov.: 33 AF XY: 0.292 AC XY: 211754 AN XY: 725564

African (AFR) AF: 0.114 AC: 3794 AN: 33416

American (AMR) AF: 0.580 AC: 25892 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 8436 AN: 26078

East Asian (EAS) AF: 0.0412 AC: 1630 AN: 39566

South Asian (SAS) AF: 0.371 AC: 31954 AN: 86168

European-Finnish (FIN) AF: 0.320 AC: 17037 AN: 53244

Middle Eastern (MID) AF: 0.289 AC: 1656 AN: 5732

European-Non Finnish (NFE) AF: 0.284 AC: 315206 AN: 1109072

Other (OTH) AF: 0.285 AC: 17133 AN: 60220

GnomAD4 genome AF: 0.249 AC: 37632 AN: 151290 Hom.: 5529 Cov.: 31 AF XY: 0.256 AC XY: 18925 AN XY: 73826

African (AFR) AF: 0.124 AC: 5100 AN: 41214

American (AMR) AF: 0.426 AC: 6450 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3472

East Asian (EAS) AF: 0.0569 AC: 294 AN: 5168

South Asian (SAS) AF: 0.371 AC: 1780 AN: 4798

European-Finnish (FIN) AF: 0.316 AC: 3255 AN: 10294

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.274 AC: 18624 AN: 67900

Other (OTH) AF: 0.269 AC: 566 AN: 2102

Alfa AF: 0.266 Hom.: 2135

Bravo AF: 0.255

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 10, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Menke-Hennekam syndrome 2 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.26
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6002271; hg19: chr22-41566595; COSMIC: COSV54331663; COSMIC: COSV54331663;