rs61756763

Variant names:

• chr22-41146749-A-G
• rs61756763
• NM_001429.4:c.2064A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-41146749-A-G
• chr22-41146749-A-C
• chr22-41146749-A-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001429.4(EP300):​c.2064A>G​(p.Leu688Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,614,102 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L688L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (13 hom.)
• Consequence: EP300 NM_001429.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.97
• Publications: 6 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-AS1 (HGNC:50504): (EP300 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 22-41146749-A-G is Benign according to our data. Variant chr22-41146749-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.97 with no splicing effect.
• BS2: High AC in GnomAd4 at 422 AD gene.

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.2064A>G	p.Leu688Leu	synonymous	Exon 11 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.2054-1088A>G		intron	N/A	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.2064A>G	p.Leu688Leu	synonymous	Exon 11 of 31	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.2064A>G	p.Leu688Leu	synonymous	Exon 11 of 31	ENSP00000586141.1
	EP300	ENST00000715703.1		c.2064A>G	p.Leu688Leu	synonymous	Exon 11 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 422 AN: 152228 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00307 AC: 772 AN: 251406 AF XY: 0.00310

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.00724

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00367 AC: 5358 AN: 1461756 Hom.: 13 Cov.: 30 AF XY: 0.00378 AC XY: 2746 AN XY: 727172

African (AFR) AF: 0.000717 AC: 24 AN: 33476

American (AMR) AF: 0.00206 AC: 92 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00777 AC: 203 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00231 AC: 199 AN: 86250

European-Finnish (FIN) AF: 0.000711 AC: 38 AN: 53412

Middle Eastern (MID) AF: 0.0116 AC: 67 AN: 5768

European-Non Finnish (NFE) AF: 0.00406 AC: 4513 AN: 1111904

Other (OTH) AF: 0.00366 AC: 221 AN: 60388

GnomAD4 genome AF: 0.00277 AC: 422 AN: 152346 Hom.: 2 Cov.: 32 AF XY: 0.00248 AC XY: 185 AN XY: 74502

African (AFR) AF: 0.000842 AC: 35 AN: 41586

American (AMR) AF: 0.00222 AC: 34 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00416 AC: 283 AN: 68036

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00447 Hom.: 2

Bravo AF: 0.00300

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	EP300-related disorder (1)
-	-	1	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.13
DANN	Benign	0.57
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs61756763; hg19: chr22-41542753; COSMIC: COSV99610246; COSMIC: COSV99610246;