rs11597888

Variant names:

• chr10-32346906-G-A
• rs11597888
• NM_001272004.3:c.10C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-32346906-G-A
• chr10-32346906-G-C
• chr10-32346906-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001272004.3(EPC1):​c.10C>T​(p.Leu4Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,613,684 control chromosomes in the GnomAD database, including 26,722 homozygotes. 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: 𝑓 0.15 (2038 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24684 hom.)
• Consequence: EPC1 NM_001272004.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 18 publications found

Genes affected

EPC1 (HGNC:19876): (enhancer of polycomb homolog 1) This gene encodes a member of the polycomb group (PcG) family. The encoded protein is a component of the NuA4 histone acetyltransferase complex and can act as both a transcriptional activator and repressor. The encoded protein has been linked to apoptosis, DNA repair, skeletal muscle differentiation, gene silencing, and adult T-cell leukemia/lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

EPC1-AS2 (HGNC:56646): (EPC1 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=2.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272004.3. 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
	EPC1	NM_001272004.3	MANE Select	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 14	NP_001258933.1
	EPC1	NM_025209.5		c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 15	NP_079485.1
	EPC1	NM_001382753.1		c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 14	NP_001369682.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPC1	ENST00000319778.11	TSL:1 MANE Select	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 14	ENSP00000318559.6
	EPC1	ENST00000263062.8	TSL:1	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 15	ENSP00000263062.8
	EPC1	ENST00000375110.6	TSL:1	c.3+31585C>T		intron	N/A	ENSP00000364251.2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22873 AN: 152126 Hom.: 2028 Cov.: 33

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.134

GnomAD2 exomes AF: 0.184 AC: 46227 AN: 250828 AF XY: 0.190

Gnomad AFR exome AF: 0.0741

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.0736

Gnomad EAS exome AF: 0.222

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.176 AC: 257767 AN: 1461438 Hom.: 24684 Cov.: 33 AF XY: 0.179 AC XY: 130476 AN XY: 727028

African (AFR) AF: 0.0732 AC: 2450 AN: 33480

American (AMR) AF: 0.218 AC: 9752 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 2001 AN: 26134

East Asian (EAS) AF: 0.269 AC: 10664 AN: 39682

South Asian (SAS) AF: 0.309 AC: 26684 AN: 86254

European-Finnish (FIN) AF: 0.176 AC: 9348 AN: 53072

Middle Eastern (MID) AF: 0.123 AC: 708 AN: 5768

European-Non Finnish (NFE) AF: 0.167 AC: 185643 AN: 1111952

Other (OTH) AF: 0.174 AC: 10517 AN: 60378

GnomAD4 genome AF: 0.150 AC: 22894 AN: 152246 Hom.: 2038 Cov.: 33 AF XY: 0.157 AC XY: 11683 AN XY: 74432

African (AFR) AF: 0.0756 AC: 3143 AN: 41558

American (AMR) AF: 0.221 AC: 3386 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 257 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1235 AN: 5160

South Asian (SAS) AF: 0.327 AC: 1579 AN: 4830

European-Finnish (FIN) AF: 0.165 AC: 1748 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11187 AN: 67996

Other (OTH) AF: 0.132 AC: 279 AN: 2112

Alfa AF: 0.146 Hom.: 1143

Bravo AF: 0.144

Asia WGS AF: 0.275 AC: 951 AN: 3478

EpiCase AF: 0.159

EpiControl AF: 0.159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.96
PhyloP100		2.9
PromoterAI		0.054	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11597888; hg19: chr10-32635834; COSMIC: COSV53928571; COSMIC: COSV53928571;