rs566063

Variant names:

• chr1-44985163-T-C
• rs566063
• NM_020365.5:c.-10+1330A>G

Variant summary

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

The NM_020365.5(EIF2B3):​c.-10+1330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,086 control chromosomes in the GnomAD database, including 8,151 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 0.31 (8151 hom., cov: 30)
• Consequence: EIF2B3 NM_020365.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 3 publications found

Genes affected

EIF2B3 (HGNC:3259): (eukaryotic translation initiation factor 2B subunit gamma) The protein encoded by this gene is one of the subunits of initiation factor eIF2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. It has also been found to function as a cofactor of hepatitis C virus internal ribosome entry site-mediated translation. Mutations in this gene have been associated with leukodystrophy with vanishing white matter. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

EIF2B3 Gene-Disease associations (from GenCC):

• leukoencephalopathy with vanishing white matter

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• leukoencephalopathy with vanishing white matter 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ovarioleukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B3	NM_020365.5	c.-10+1330A>G		intron_variant	Intron 1 of 11	ENST00000360403.7	NP_065098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B3	ENST00000360403.7	c.-10+1330A>G		intron_variant	Intron 1 of 11	1	NM_020365.5	ENSP00000353575.2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47078 AN: 151966 Hom.: 8141 Cov.: 30

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.310 AC: 47117 AN: 152086 Hom.: 8151 Cov.: 30 AF XY: 0.307 AC XY: 22792 AN XY: 74338

African (AFR) AF: 0.449 AC: 18600 AN: 41462

American (AMR) AF: 0.360 AC: 5499 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1420 AN: 5166

South Asian (SAS) AF: 0.201 AC: 968 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2318 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16630 AN: 67978

Other (OTH) AF: 0.297 AC: 628 AN: 2114

Alfa AF: 0.276 Hom.: 2176

Bravo AF: 0.327

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		-0.26
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: rs566063; hg19: chr1-45450835;