rs6587216

Variant names:

• chr17-19321084-G-C
• rs6587216
• NM_014964.5:c.1148-7627G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014964.5(EPN2):​c.1148-7627G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,114 control chromosomes in the GnomAD database, including 42,622 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 0.73 (42622 hom., cov: 32)
• Consequence: EPN2 NM_014964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 8 publications found

Genes affected

EPN2 (HGNC:18639): (epsin 2) This gene encodes a protein which interacts with clathrin and adaptor-related protein complex 2, alpha 1 subunit. The protein is found in a brain-derived clathrin-coated vesicle fraction and localizes to the peri-Golgi region and the cell periphery. The protein is thought to be involved in clathrin-mediated endocytosis. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014964.5. 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
	EPN2	NM_014964.5	MANE Select	c.1148-7627G>C		intron	N/A	NP_055779.2	O95208-1
	EPN2	NM_148921.4		c.977-7627G>C		intron	N/A	NP_683723.2	O95208-2
	EPN2	NM_001102664.2		c.293-7627G>C		intron	N/A	NP_001096134.1	O95208-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPN2	ENST00000314728.10	TSL:1 MANE Select	c.1148-7627G>C		intron	N/A	ENSP00000320543.5	O95208-1
	EPN2	ENST00000395620.6	TSL:1	c.977-7627G>C		intron	N/A	ENSP00000378982.2	O95208-2
	EPN2	ENST00000571254.1	TSL:1	c.956-7627G>C		intron	N/A	ENSP00000459542.1	I3L2B2

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111037 AN: 151996 Hom.: 42605 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.738

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.730 AC: 111091 AN: 152114 Hom.: 42622 Cov.: 32 AF XY: 0.715 AC XY: 53156 AN XY: 74352

African (AFR) AF: 0.747 AC: 31003 AN: 41484

American (AMR) AF: 0.607 AC: 9269 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2900 AN: 3468

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5178

South Asian (SAS) AF: 0.406 AC: 1957 AN: 4818

European-Finnish (FIN) AF: 0.775 AC: 8212 AN: 10590

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 55037 AN: 67990

Other (OTH) AF: 0.729 AC: 1538 AN: 2110

Alfa AF: 0.784 Hom.: 5229

Bravo AF: 0.720

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		-0.51
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6587216;

hg19: chr17-19224397;