22-41093139-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001429.4(EP300):c.94+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,581,908 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: EP300 NM_001429.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.196

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-41093139-C-T is Benign according to our data. Variant chr22-41093139-C-T is described in ClinVar as [Benign]. Clinvar id is 1289013.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 166 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EP300	NM_001429.4	c.94+41C>T		intron_variant		ENST00000263253.9
EP300	NM_001362843.2	c.94+41C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EP300	ENST00000263253.9	c.94+41C>T		intron_variant		1	NM_001429.4	P2
EP300	ENST00000674155.1	c.94+41C>T		intron_variant				A2
EP300	ENST00000703544.1	c.94+41C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000922 AC: 227 AN: 246080 Hom.: 0 AF XY: 0.000919 AC XY: 123 AN XY: 133872

Gnomad AFR exome AF: 0.0000639

Gnomad AMR exome AF: 0.000552

Gnomad ASJ exome AF: 0.00100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00153 AC: 2192 AN: 1429598 Hom.: 2 Cov.: 25 AF XY: 0.00153 AC XY: 1089 AN XY: 712978

Gnomad4 AFR exome AF: 0.000183

Gnomad4 AMR exome AF: 0.000627

Gnomad4 ASJ exome AF: 0.000618

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.000207

Gnomad4 NFE exome AF: 0.00190

Gnomad4 OTH exome AF: 0.00115

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74476

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.000990

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 16, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.2
Dann	Benign	0.79

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: rs201866159; hg19: chr22-41489143;