chr22-41170591-C-T

Variant names:

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

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.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

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]

ENSG00000232754 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 93741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41170591-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.4452+20C>T		intron_variant	Intron 27 of 30	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.4374+20C>T		intron_variant	Intron 26 of 29		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.4452+20C>T		intron_variant	Intron 27 of 30	1	NM_001429.4	ENSP00000263253.7
EP300	ENST00000674155.1	c.4374+20C>T		intron_variant	Intron 26 of 29			ENSP00000501078.1
ENSG00000232754	ENST00000415054.1	n.83-1010G>A		intron_variant	Intron 1 of 2	3
EP300	ENST00000703544.1	n.*2372+20C>T		intron_variant	Intron 26 of 29			ENSP00000515365.1

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

GnomAD3 exomes AF: 0.314 AC: 78725 AN: 250960 Hom.: 15077 AF XY: 0.311 AC XY: 42223 AN XY: 135706

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 SAS exome AF: 0.368

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

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.0412

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.285

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

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.0569

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.269

Alfa AF: 0.267 Hom.: 1257

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

Jun 10, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.26
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: rs6002271; hg19: chr22-41566595; COSMIC: COSV54331663; COSMIC: COSV54331663;