22-41093056-C-G

Variant names:

• chr22-41093056-C-G
• rs777392825
• NM_001429.4:c.52C>G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_001429.4(EP300):​c.52C>G​(p.Leu18Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: EP300 NM_001429.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.81

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40559486).
• BP6: Variant 22-41093056-C-G is Benign according to our data. Variant chr22-41093056-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3661913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.52C>G	p.Leu18Val	missense_variant	Exon 1 of 31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.52C>G	p.Leu18Val	missense_variant	Exon 1 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.52C>G	p.Leu18Val	missense_variant	Exon 1 of 31	1	NM_001429.4	ENSP00000263253.7
EP300	ENST00000674155.1	c.52C>G	p.Leu18Val	missense_variant	Exon 1 of 30			ENSP00000501078.1
EP300	ENST00000703544.1	n.52C>G		non_coding_transcript_exon_variant	Exon 1 of 30			ENSP00000515365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250958 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.061	T
Polyphen		0.99	D
Vest4		0.43
MutPred		0.15		Loss of loop (P = 0.0603);
MVP		0.83
ClinPred		0.97	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.52
gMVP		0.24

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: rs777392825; hg19: chr22-41489060;