rs1043809

Variant names:

• chr17-19336119-C-T
• rs1043809
• NM_014964.5:c.*1865C>T

Variant summary

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

The NM_014964.5(EPN2):​c.*1865C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,198 control chromosomes in the GnomAD database, including 30,697 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 0.56 (30683 hom., cov: 32)
  • Exomes 𝑓: 0.66 (14 hom.)
• Consequence: EPN2 NM_014964.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

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]

B9D1 (HGNC:24123): (B9 domain containing 1) This gene encodes a B9 domain-containing protein, one of several that are involved in ciliogenesis. Alterations in expression of this gene have been found in a family with Meckel syndrome. Meckel syndrome has been associated with at least six different genes. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Mar 2016]

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 (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPN2	NM_014964.5	c.*1865C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000314728.10	NP_055779.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPN2	ENST00000314728.10	c.*1865C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_014964.5	ENSP00000320543.5

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84594 AN: 152022 Hom.: 30689 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.655 AC: 38 AN: 58 Hom.: 14 Cov.: 0 AF XY: 0.720 AC XY: 36 AN XY: 50

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.556 AC: 84577 AN: 152140 Hom.: 30683 Cov.: 32 AF XY: 0.545 AC XY: 40541 AN XY: 74362

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.609

Alfa AF: 0.732 Hom.: 48512

Bravo AF: 0.523

Asia WGS AF: 0.168 AC: 585 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	0.63
DANN	Benign	0.54

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: rs1043809; hg19: chr17-19239432;