rs11597888

chr10-32346906-G-Achr10-32346906-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001272004.3(EPC1):c.10C>T(p.Leu4=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPC1	NM_001272004.3	c.10C>T	p.Leu4=	synonymous_variant	1/14	ENST00000319778.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPC1	ENST00000319778.11	c.10C>T	p.Leu4=	synonymous_variant	1/14	1	NM_001272004.3	P1
EPC1-AS2	ENST00000412085.1	n.110G>A		non_coding_transcript_exon_variant	2/2	5

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

GnomAD3 exomes AF: 0.184 AC: 46227 AN: 250828 Hom.: 4837 AF XY: 0.190 AC XY: 25732 AN XY: 135676

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 SAS exome AF: 0.312

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

Gnomad4 AFR exome AF: 0.0732

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.174

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

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.132

Alfa AF: 0.146 Hom.: 876

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	20
Dann	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs11597888; hg19: chr10-32635834; COSMIC: COSV53928571; COSMIC: COSV53928571;