Genetic Variant EPC1:p.Leu4Leu (chr10-32346906-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Publications

18 publications found

Variant links:

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 links:

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

EPC1-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPC1	NM_001272004.3 link	c.10C>T	p.Leu4Leu	synonymous_variant	Exon 1 of 14	ENST00000319778.11	NP_001258933.1	Q9H2F5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPC1	ENST00000319778.11 link	c.10C>T	p.Leu4Leu	synonymous_variant	Exon 1 of 14	1	NM_001272004.3	ENSP00000318559.6		Q9H2F5-2

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22873

AN:

152126

Hom.:

2028

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.179

AC XY:

130476

AN XY:

727028

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

12388

24777

37165

49554

61942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6824

13648

20472

27296

34120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.150

AC:

22894

AN:

152246

Hom.:

2038

Cov.:

AF XY:

0.157

AC XY:

11683

AN XY:

74432

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11187

AN:

67996

Other (OTH)

AF:

0.132

AC:

279

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1004

2008

3011

4015

5019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

2.9

PromoterAI

0.054

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over