chr3-5219976-T-C

Position:

• chr3-5219976-T-C

Variant summary

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

The 3-5219976-T-C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,358 control chromosomes in the GnomAD database, including 67,638 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 0.94 (67604 hom., cov: 33)
  • Exomes 𝑓: 0.96 (34 hom.)
• Consequence: EDEM1 ENST00000256497.9 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDEM1	NM_014674.3			downstream_gene_variant		ENST00000256497.9	NP_055489.1
EDEM1	XM_011534272.3			downstream_gene_variant			XP_011532574.1
EDEM1	XM_047449266.1			downstream_gene_variant			XP_047305222.1
EDEM1	XM_047449267.1			downstream_gene_variant			XP_047305223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM1	ENST00000256497.9			downstream_gene_variant		1	NM_014674.3	ENSP00000256497	P1

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143174 AN: 152166 Hom.: 67568 Cov.: 33

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.962

GnomAD4 exome AF: 0.959 AC: 71 AN: 74 Hom.: 34 Cov.: 0 AF XY: 0.979 AC XY: 47 AN XY: 48

Gnomad4 FIN exome AF: 0.958

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.941 AC: 143267 AN: 152284 Hom.: 67604 Cov.: 33 AF XY: 0.939 AC XY: 69901 AN XY: 74450

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.962

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.957

Alfa AF: 0.954 Hom.: 10419

Bravo AF: 0.940

Asia WGS AF: 0.887 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs457712; hg19: chr3-5261661;