rs10508773

Variant names:

• chr10-32286516-C-T
• rs10508773
• NM_001272004.3:c.1391+178G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPC1	NM_001272004.3	c.1391+178G>A		intron_variant	Intron 9 of 13	ENST00000319778.11	NP_001258933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPC1	ENST00000319778.11	c.1391+178G>A		intron_variant	Intron 9 of 13	1	NM_001272004.3	ENSP00000318559.6

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

African (AFR) AF: 0.0968 AC: 1402 AN: 14486

American (AMR) AF: 0.221 AC: 3911 AN: 17722

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 1032 AN: 13870

East Asian (EAS) AF: 0.277 AC: 8622 AN: 31172

South Asian (SAS) AF: 0.298 AC: 11636 AN: 39020

European-Finnish (FIN) AF: 0.174 AC: 5186 AN: 29832

Middle Eastern (MID) AF: 0.120 AC: 255 AN: 2120

European-Non Finnish (NFE) AF: 0.164 AC: 60884 AN: 372302

Other (OTH) AF: 0.168 AC: 4881 AN: 29052

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

African (AFR) AF: 0.0982 AC: 4076 AN: 41500

American (AMR) AF: 0.223 AC: 3412 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1226 AN: 5174

South Asian (SAS) AF: 0.326 AC: 1571 AN: 4816

European-Finnish (FIN) AF: 0.164 AC: 1734 AN: 10568

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11203 AN: 68000

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.160 Hom.: 3434

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs10508773; hg19: chr10-32575444;