rs2370759

Variant names:

• chr10-32346044-G-A
• rs2370759
• NM_001272004.3:c.153+719C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001272004.3(EPC1):​c.153+719C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,868 control chromosomes in the GnomAD database, including 2,040 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 (2040 hom., cov: 32)
• Consequence: EPC1 NM_001272004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 15 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=-0.76).
• 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 rank	MANE	Protein	UniProt
EPC1	NM_001272004.3	c.153+719C>T		intron_variant	Intron 1 of 13	ENST00000319778.11	NP_001258933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPC1	ENST00000319778.11	c.153+719C>T		intron_variant	Intron 1 of 13	1	NM_001272004.3	ENSP00000318559.6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22866 AN: 151750 Hom.: 2031 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 22885 AN: 151868 Hom.: 2040 Cov.: 32 AF XY: 0.157 AC XY: 11678 AN XY: 74264

African (AFR) AF: 0.0761 AC: 3136 AN: 41194

American (AMR) AF: 0.221 AC: 3380 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1235 AN: 5170

South Asian (SAS) AF: 0.328 AC: 1582 AN: 4830

European-Finnish (FIN) AF: 0.165 AC: 1748 AN: 10608

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

European-Non Finnish (NFE) AF: 0.165 AC: 11186 AN: 67996

Other (OTH) AF: 0.134 AC: 282 AN: 2108

Alfa AF: 0.156 Hom.: 7169

Bravo AF: 0.144

Asia WGS AF: 0.274 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		-0.26
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: rs2370759; hg19: chr10-32634972;