rs10508773

chr10-32286516-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001272004.3(EPC1):c.1391+178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 701,706 control chromosomes in the GnomAD database, including 11,919 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 0.16 (2125 hom., cov: 32)
  • Exomes 𝑓: 0.18 (9794 hom.)
• Consequence: EPC1 NM_001272004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPC1	NM_001272004.3	c.1391+178G>A		intron_variant		ENST00000319778.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPC1	ENST00000319778.11	c.1391+178G>A		intron_variant		1	NM_001272004.3	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23818 AN: 152012 Hom.: 2113 Cov.: 32

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.178 AC: 97809 AN: 549576 Hom.: 9794 Cov.: 8 AF XY: 0.182 AC XY: 51071 AN XY: 281310

Gnomad4 AFR exome AF: 0.0968

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.0744

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.157 AC: 23854 AN: 152130 Hom.: 2125 Cov.: 32 AF XY: 0.163 AC XY: 12122 AN XY: 74364

Gnomad4 AFR AF: 0.0982

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.139

Alfa AF: 0.161 Hom.: 2748

Bravo AF: 0.152

Asia WGS AF: 0.279 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.7
Dann	Benign	0.60

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: rs10508773; hg19: chr10-32575444;