NM_001429.4:c.27G>C

Variant names:

• chr22-41093031-G-C
• rs2145665487
• NM_001429.4:c.27G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001429.4(EP300):​c.27G>C​(p.Gly9Gly) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EP300 NM_001429.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.74
• Publications: 0 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 Gene-Disease associations (from GenCC):

• Rubinstein-Taybi syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• retinitis pigmentosa

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000296654 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 22-41093031-G-C is Benign according to our data. Variant chr22-41093031-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3344089.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	NM_001429.4	MANE Select	c.27G>C	p.Gly9Gly	synonymous	Exon 1 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.27G>C	p.Gly9Gly	synonymous	Exon 1 of 30	NP_001349772.1	A0A669KB12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EP300	ENST00000263253.9	TSL:1 MANE Select	c.27G>C	p.Gly9Gly	synonymous	Exon 1 of 31	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.27G>C	p.Gly9Gly	synonymous	Exon 1 of 31	ENSP00000586141.1
	EP300	ENST00000715703.1		c.27G>C	p.Gly9Gly	synonymous	Exon 1 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EP300-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		4.7
PromoterAI		0.055	Neutral

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: rs2145665487; hg19: chr22-41489035;