rs726427

Positions:

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

Variant summary

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

The ENST00000318130.13(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 ENST00000318130.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EDEM3	NM_025191.4	c.2390-1987G>T		intron_variant		ENST00000318130.13	NP_079467.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM3	ENST00000318130.13	c.2390-1987G>T		intron_variant		1	NM_025191.4	ENSP00000318147	P4

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

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.417

Alfa AF: 0.382 Hom.: 3200

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

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: rs726427; hg19: chr1-184665593;