22-41178956-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_001429.4(EP300):​c.7245G>C​(p.Ter2415Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

EP300
NM_001429.4 stop_lost

Scores

2
1
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_001429.4 Downstream stopcodon found after 2551 codons.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EP300NM_001429.4 linkc.7245G>C p.Ter2415Tyrext*? stop_lost Exon 31 of 31 ENST00000263253.9 NP_001420.2 Q09472Q7Z6C1
EP300NM_001362843.2 linkc.7167G>C p.Ter2389Tyrext*? stop_lost Exon 30 of 30 NP_001349772.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EP300ENST00000263253.9 linkc.7245G>C p.Ter2415Tyrext*? stop_lost Exon 31 of 31 1 NM_001429.4 ENSP00000263253.7 Q09472
EP300ENST00000674155.1 linkc.7167G>C p.Ter2389Tyrext*? stop_lost Exon 30 of 30 ENSP00000501078.1 A0A669KB12
ENSG00000232754ENST00000415054.1 linkn.82+4107C>G intron_variant Intron 1 of 2 3
EP300-AS1ENST00000420537.1 linkn.224-4132C>G intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
16
DANN
Benign
0.88
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Uncertain
0.95
D
Vest4
0.24
GERP RS
5.5

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-41574960; COSMIC: COSV54343900; COSMIC: COSV54343900; API