dbSNP rs2306001: EPN3: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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPN3	NM_017957.3 link	c.563-111G>A		intron_variant	Intron 2 of 9	ENST00000268933.8	NP_060427.2
LOC105371824	NR_135675.1 link	n.358C>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPN3	ENST00000268933.8 link	c.563-111G>A		intron_variant	Intron 2 of 9	2	NM_017957.3	ENSP00000268933.3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over