rs410509

Positions:

• chr3-5199624-C-A
• chr3-5199624-C-G
• chr3-5199624-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000256497.9(EDEM1):​c.615C>A​(p.Ala205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 1,613,392 control chromosomes in the GnomAD database, including 752,632 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 0.95 (68148 hom., cov: 33)
  • Exomes 𝑓: 0.97 (684484 hom.)
• Consequence: EDEM1 ENST00000256497.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

Genes affected

EDEM1 (HGNC:18967): (ER degradation enhancing alpha-mannosidase like protein 1) Enables mannosyl-oligosaccharide 1,2-alpha-mannosidase activity and misfolded protein binding activity. Involved in mannose trimming involved in glycoprotein ERAD pathway; positive regulation of retrograde protein transport, ER to cytosol; and protein targeting to ER. Located in aggresome and endoplasmic reticulum quality control compartment. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDEM1	NM_014674.3	c.615C>A	p.Ala205=	synonymous_variant	3/12	ENST00000256497.9	NP_055489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM1	ENST00000256497.9	c.615C>A	p.Ala205=	synonymous_variant	3/12	1	NM_014674.3	ENSP00000256497	P1

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143839 AN: 152172 Hom.: 68110 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.960

GnomAD3 exomes AF: 0.959 AC: 240508 AN: 250906 Hom.: 115472 AF XY: 0.958 AC XY: 129855 AN XY: 135618

Gnomad AFR exome AF: 0.878

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.971

Gnomad EAS exome AF: 0.940

Gnomad SAS exome AF: 0.894

Gnomad FIN exome AF: 0.988

Gnomad NFE exome AF: 0.975

Gnomad OTH exome AF: 0.968

GnomAD4 exome AF: 0.968 AC: 1413686 AN: 1461102 Hom.: 684484 Cov.: 40 AF XY: 0.966 AC XY: 701952 AN XY: 726874

Gnomad4 AFR exome AF: 0.874

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.968

Gnomad4 EAS exome AF: 0.945

Gnomad4 SAS exome AF: 0.900

Gnomad4 FIN exome AF: 0.986

Gnomad4 NFE exome AF: 0.975

Gnomad4 OTH exome AF: 0.961

GnomAD4 genome AF: 0.945 AC: 143935 AN: 152290 Hom.: 68148 Cov.: 33 AF XY: 0.944 AC XY: 70338 AN XY: 74478

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.970

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.956

Alfa AF: 0.967 Hom.: 88281

Bravo AF: 0.943

Asia WGS AF: 0.893 AC: 3106 AN: 3478

EpiCase AF: 0.978

EpiControl AF: 0.974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	4.4
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs410509; hg19: chr3-5241309;