1-184696459-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_025191.4(EDEM3):​c.2390-1987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 151,504 control chromosomes in the GnomAD database, including 3 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 0.0012 (3 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: ClinGen, 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=-0.96).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00117 (178/151504) while in subpopulation EAS AF = 0.0299 (154/5150). AF 95% confidence interval is 0.0261. There are 3 homozygotes in GnomAd4. There are 108 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025191.4. 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
	EDEM3	NM_025191.4	MANE Select	c.2390-1987G>A		intron	N/A	NP_079467.3
	EDEM3	NM_001319960.2		c.2438-1987G>A		intron	N/A	NP_001306889.1	A0A8J8YX80
	EDEM3	NR_135118.2		n.2669-1987G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM3	ENST00000318130.13	TSL:1 MANE Select	c.2390-1987G>A		intron	N/A	ENSP00000318147.7	Q9BZQ6-1
	EDEM3	ENST00000367512.8	TSL:1	c.2438-1987G>A		intron	N/A	ENSP00000356482.4	A0A8J8YX80
	EDEM3	ENST00000439962.1	TSL:1	n.734-1987G>A		intron	N/A	ENSP00000390536.1	H0Y498

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 181 AN: 151386 Hom.: 3 Cov.: 30

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.00376

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00117 AC: 178 AN: 151504 Hom.: 3 Cov.: 30 AF XY: 0.00146 AC XY: 108 AN XY: 73990

African (AFR) AF: 0.0000242 AC: 1 AN: 41354

American (AMR) AF: 0.0000659 AC: 1 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.0299 AC: 154 AN: 5150

South Asian (SAS) AF: 0.00377 AC: 18 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000590 AC: 4 AN: 67768

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000220 Hom.: 3886

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.82
DANN	Benign	0.93
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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;