Genetic Variant NM_017957.3:c.563-111G>A (chr17-50537968-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017957.3(EPN3):c.563-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 900,114 control chromosomes in the GnomAD database, including 4,303 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 0.070 ( 498 hom., cov: 33)

Exomes 𝑓: 0.094 ( 3805 hom. )

Consequence

EPN3
NM_017957.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

12 publications found

Variant links:

Genes affected

EPN3 (HGNC:18235): (epsin 3) Predicted to enable clathrin binding activity and phospholipid binding activity. Predicted to be involved in endocytosis. Located in clathrin-coated vesicle; nucleoplasm; and perinuclear region of cytoplasm. Is extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EPN3 links:

ENSG00000250286 (HGNC:):

ENSG00000250286 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017957.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPN3	NM_017957.3	MANE Select	c.563-111G>A		intron	N/A	NP_060427.2
	LOC105371824	NR_135675.1		n.358C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EPN3	ENST00000268933.8	TSL:2 MANE Select	c.563-111G>A	intron	N/A	ENSP00000268933.3
ENSG00000250286	ENST00000509260.1	TSL:3	n.473C>T	non_coding_transcript_exon	Exon 1 of 2
ENSG00000250286	ENST00000513017.1	TSL:3	n.358C>T	non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10630

AN:

152206

Hom.:

499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0431

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.0492

Gnomad FIN

AF:

0.0914

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0554

GnomAD4 exome

AF:

0.0936

AC:

69969

AN:

747790

Hom.:

3805

Cov.:

AF XY:

0.0923

AC XY:

35858

AN XY:

388360

show subpopulations

African (AFR)

AF:

0.0175

AC:

331

AN:

18948

American (AMR)

AF:

0.0326

AC:

1086

AN:

33352

Ashkenazi Jewish (ASJ)

AF:

0.0423

AC:

728

AN:

17198

East Asian (EAS)

AF:

0.0291

AC:

1017

AN:

34970

South Asian (SAS)

AF:

0.0531

AC:

3198

AN:

60184

European-Finnish (FIN)

AF:

0.0961

AC:

4204

AN:

43764

Middle Eastern (MID)

AF:

0.0394

AC:

164

AN:

4166

European-Non Finnish (NFE)

AF:

0.113

AC:

56317

AN:

499070

Other (OTH)

AF:

0.0809

AC:

2924

AN:

36138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3156

6311

9467

12622

15778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1280

2560

3840

5120

6400

<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:

0.0697

AC:

10624

AN:

152324

Hom.:

498

Cov.:

AF XY:

0.0685

AC XY:

5099

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0192

AC:

797

AN:

41576

American (AMR)

AF:

0.0429

AC:

657

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

149

AN:

3472

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5182

South Asian (SAS)

AF:

0.0491

AC:

237

AN:

4830

European-Finnish (FIN)

AF:

0.0914

AC:

971

AN:

10624

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7536

AN:

68010

Other (OTH)

AF:

0.0543

AC:

115

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

500

1000

1501

2001

2501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0928

Hom.:

269

Bravo

AF:

0.0642

Asia WGS

AF:

0.0320

AC:

113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.8

(source)

DANN

Benign

0.75

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over