rs2306002

Positions:

• chr17-50540468-G-A
• chr17-50540468-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017957.3(EPN3):​c.979+134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 806,988 control chromosomes in the GnomAD database, including 129,288 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 0.60 (29382 hom., cov: 33)
  • Exomes 𝑓: 0.54 (99906 hom.)
• Consequence: EPN3 NM_017957.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPN3	NM_017957.3	c.979+134G>A		intron_variant		ENST00000268933.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPN3	ENST00000268933.8	c.979+134G>A		intron_variant		2	NM_017957.3	P1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91859 AN: 152018 Hom.: 29337 Cov.: 33

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.537 AC: 351743 AN: 654852 Hom.: 99906 AF XY: 0.530 AC XY: 177730 AN XY: 335322

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.761

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.604 AC: 91964 AN: 152136 Hom.: 29382 Cov.: 33 AF XY: 0.592 AC XY: 44004 AN XY: 74362

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.614

Alfa AF: 0.342 Hom.: 672

Bravo AF: 0.626

Asia WGS AF: 0.317 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306002; hg19: chr17-48617829;