rs34985152

Variant names:

• chr22-41178083-C-T
• rs34985152
• NM_001429.4:c.6372C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-41178083-C-T
• chr22-41178083-C-A
• chr22-41178083-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001429.4(EP300):​c.6372C>T​(p.Val2124Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,614,102 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (60 hom.)
• Consequence: EP300 NM_001429.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.257
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 22-41178083-C-T is Benign according to our data. Variant chr22-41178083-C-T is described in ClinVar as Benign. ClinVar VariationId is 158568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.257 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

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.6372C>T	p.Val2124Val	synonymous	Exon 31 of 31	NP_001420.2	Q09472
	EP300	NM_001362843.2		c.6294C>T	p.Val2098Val	synonymous	Exon 30 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.6372C>T	p.Val2124Val	synonymous	Exon 31 of 31	ENSP00000263253.7	Q09472
	EP300	ENST00000916082.1		c.6402C>T	p.Val2134Val	synonymous	Exon 31 of 31	ENSP00000586141.1
	EP300	ENST00000715703.1		c.6372C>T	p.Val2124Val	synonymous	Exon 31 of 31	ENSP00000520505.1	Q09472

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2371 AN: 152146 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00549

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00417 AC: 1047 AN: 251284 AF XY: 0.00314

Gnomad AFR exome AF: 0.0551

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00167 AC: 2442 AN: 1461838 Hom.: 60 Cov.: 31 AF XY: 0.00147 AC XY: 1068 AN XY: 727214

African (AFR) AF: 0.0552 AC: 1847 AN: 33478

American (AMR) AF: 0.00342 AC: 153 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.000156 AC: 174 AN: 1111972

Other (OTH) AF: 0.00384 AC: 232 AN: 60392

GnomAD4 genome AF: 0.0156 AC: 2376 AN: 152264 Hom.: 57 Cov.: 32 AF XY: 0.0155 AC XY: 1157 AN XY: 74436

African (AFR) AF: 0.0541 AC: 2247 AN: 41536

American (AMR) AF: 0.00549 AC: 84 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68020

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.00764 Hom.: 26

Bravo AF: 0.0175

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.5
DANN	Benign	0.86
PhyloP100		0.26
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: rs34985152; hg19: chr22-41574087;