17-50536476-A-G

Variant names:

• chr17-50536476-A-G
• rs3785915
• NM_017957.3:c.-81A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017957.3(EPN3):​c.-81A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,588,294 control chromosomes in the GnomAD database, including 415,355 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 0.75 (43480 hom., cov: 30)
  • Exomes 𝑓: 0.72 (371875 hom.)
• Consequence: EPN3 NM_017957.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 28 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]

ENSG00000250286 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.043).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPN3	NM_017957.3	MANE Select	c.-81A>G		5_prime_UTR	Exon 2 of 10	NP_060427.2	Q9H201-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPN3	ENST00000268933.8	TSL:2 MANE Select	c.-81A>G		5_prime_UTR	Exon 2 of 10	ENSP00000268933.3	Q9H201-1
	EPN3	ENST00000883554.1		c.-81A>G		5_prime_UTR	Exon 3 of 11	ENSP00000553613.1
	EPN3	ENST00000883556.1		c.-81A>G		5_prime_UTR	Exon 2 of 10	ENSP00000553615.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114307 AN: 151710 Hom.: 43448 Cov.: 30

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.757

GnomAD2 exomes AF: 0.748 AC: 166331 AN: 222346 AF XY: 0.740

Gnomad AFR exome AF: 0.833

Gnomad AMR exome AF: 0.799

Gnomad ASJ exome AF: 0.838

Gnomad EAS exome AF: 0.920

Gnomad FIN exome AF: 0.687

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.717 AC: 1030597 AN: 1436464 Hom.: 371875 Cov.: 66 AF XY: 0.716 AC XY: 511949 AN XY: 715084

African (AFR) AF: 0.838 AC: 26950 AN: 32154

American (AMR) AF: 0.794 AC: 31689 AN: 39906

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 21010 AN: 25196

East Asian (EAS) AF: 0.924 AC: 36554 AN: 39580

South Asian (SAS) AF: 0.704 AC: 58910 AN: 83718

European-Finnish (FIN) AF: 0.687 AC: 30788 AN: 44836

Middle Eastern (MID) AF: 0.765 AC: 4330 AN: 5658

European-Non Finnish (NFE) AF: 0.702 AC: 776564 AN: 1105984

Other (OTH) AF: 0.737 AC: 43802 AN: 59432

GnomAD4 genome AF: 0.753 AC: 114393 AN: 151830 Hom.: 43480 Cov.: 30 AF XY: 0.753 AC XY: 55847 AN XY: 74182

African (AFR) AF: 0.830 AC: 34353 AN: 41400

American (AMR) AF: 0.784 AC: 11971 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2898 AN: 3472

East Asian (EAS) AF: 0.912 AC: 4656 AN: 5104

South Asian (SAS) AF: 0.704 AC: 3387 AN: 4808

European-Finnish (FIN) AF: 0.676 AC: 7136 AN: 10552

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47478 AN: 67906

Other (OTH) AF: 0.759 AC: 1603 AN: 2112

Alfa AF: 0.725 Hom.: 133858

Bravo AF: 0.770

Asia WGS AF: 0.811 AC: 2822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.050
DANN	Benign	0.31
PhyloP100		-2.6
Mutation Taster		=291/9	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: rs3785915; hg19: chr17-48613837; COSMIC: COSV52137391; COSMIC: COSV52137391;