ENST00000360403:c.*282G>A

Variant names:

• chr1-44850669-C-T
• rs991449922
• NM_020365.5:c.*282G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000360403.7(EIF2B3):​c.*282G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 504,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: EIF2B3 ENST00000360403.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.47
• Publications: 0 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 3

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360403.7. 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
	EIF2B3	NM_020365.5	MANE Select	c.*282G>A		3_prime_UTR	Exon 12 of 12	NP_065098.1	Q9NR50-1
	EIF2B3	NM_001261418.2		c.*331G>A		3_prime_UTR	Exon 11 of 11	NP_001248347.1	Q9NR50-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B3	ENST00000360403.7	TSL:1 MANE Select	c.*282G>A		3_prime_UTR	Exon 12 of 12	ENSP00000353575.2	Q9NR50-1
	EIF2B3	ENST00000620860.4	TSL:1	c.*331G>A		3_prime_UTR	Exon 11 of 11	ENSP00000483996.1	Q9NR50-3
	EIF2B3	ENST00000852384.1		c.*282G>A		downstream_gene	N/A	ENSP00000522443.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000510 AC: 18 AN: 352678 Hom.: 0 Cov.: 0 AF XY: 0.0000538 AC XY: 10 AN XY: 185908

African (AFR) AF: 0.00 AC: 0 AN: 10288

American (AMR) AF: 0.00 AC: 0 AN: 14156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10778

East Asian (EAS) AF: 0.000731 AC: 17 AN: 23246

South Asian (SAS) AF: 0.00 AC: 0 AN: 37238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1494

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 213314

Other (OTH) AF: 0.0000490 AC: 1 AN: 20420

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Vanishing white matter disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.56
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs991449922; hg19: chr1-45316341;