rs726427

Variant names:

• chr1-184696459-C-A
• rs726427
• NM_025191.4:c.2390-1987G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-184696459-C-A
• chr1-184696459-C-T

Variant summary

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

The NM_025191.4(EDEM3):​c.2390-1987G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,400 control chromosomes in the GnomAD database, including 12,684 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 0.40 (12684 hom., cov: 30)
• Consequence: EDEM3 NM_025191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 6 publications found

Genes affected

EDEM3 (HGNC:16787): (ER degradation enhancing alpha-mannosidase like protein 3) Quality control in the endoplasmic reticulum (ER) ensures that only properly folded proteins are retained in the cell through recognition and degradation of misfolded or unassembled proteins. EDEM3 belongs to a group of proteins that accelerate degradation of misfolded glycoproteins in the ER (Hirao et al., 2006 [PubMed 16431915]).[supplied by OMIM, Mar 2008]

EDEM3 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type 2v

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDEM3	NM_025191.4	c.2390-1987G>T		intron_variant	Intron 19 of 19	ENST00000318130.13	NP_079467.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDEM3	ENST00000318130.13	c.2390-1987G>T		intron_variant	Intron 19 of 19	1	NM_025191.4	ENSP00000318147.7

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60449 AN: 151282 Hom.: 12680 Cov.: 30

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.399 AC: 60477 AN: 151400 Hom.: 12684 Cov.: 30 AF XY: 0.404 AC XY: 29892 AN XY: 73938

African (AFR) AF: 0.266 AC: 10997 AN: 41332

American (AMR) AF: 0.406 AC: 6161 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1567 AN: 3464

East Asian (EAS) AF: 0.595 AC: 3062 AN: 5142

South Asian (SAS) AF: 0.589 AC: 2808 AN: 4770

European-Finnish (FIN) AF: 0.446 AC: 4680 AN: 10504

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29719 AN: 67730

Other (OTH) AF: 0.417 AC: 874 AN: 2094

Alfa AF: 0.392 Hom.: 3886

Bravo AF: 0.390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.37
PhyloP100		-0.30
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: rs726427; hg19: chr1-184665593;