rs2306002

Variant names:

• chr17-50540468-G-A
• rs2306002
• NM_017957.3:c.979+134G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPN3	NM_017957.3	c.979+134G>A		intron_variant	Intron 6 of 9	ENST00000268933.8	NP_060427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPN3	ENST00000268933.8	c.979+134G>A		intron_variant	Intron 6 of 9	2	NM_017957.3	ENSP00000268933.3

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

African (AFR) AF: 0.794 AC: 12993 AN: 16356

American (AMR) AF: 0.556 AC: 12254 AN: 22048

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 11692 AN: 15358

East Asian (EAS) AF: 0.137 AC: 4379 AN: 31896

South Asian (SAS) AF: 0.375 AC: 19629 AN: 52302

European-Finnish (FIN) AF: 0.492 AC: 15219 AN: 30930

Middle Eastern (MID) AF: 0.638 AC: 1694 AN: 2654

European-Non Finnish (NFE) AF: 0.567 AC: 255322 AN: 450362

Other (OTH) AF: 0.563 AC: 18561 AN: 32946

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

African (AFR) AF: 0.785 AC: 32578 AN: 41506

American (AMR) AF: 0.582 AC: 8898 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2642 AN: 3466

East Asian (EAS) AF: 0.145 AC: 750 AN: 5174

South Asian (SAS) AF: 0.332 AC: 1604 AN: 4826

European-Finnish (FIN) AF: 0.472 AC: 4996 AN: 10578

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38385 AN: 67976

Other (OTH) AF: 0.614 AC: 1298 AN: 2114

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
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2306002; hg19: chr17-48617829;