NM_001414.4:c.*464A>C

Variant names:

• chr12-123621292-T-G
• rs9919
• NM_001414.4:c.*464A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001414.4(EIF2B1):​c.*464A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF2B1 NM_001414.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 12 publications found

Genes affected

EIF2B1 (HGNC:3257): (eukaryotic translation initiation factor 2B subunit alpha) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Oct 2009]

EIF2B1 Gene-Disease associations (from GenCC):

• leukoencephalopathy with vanishing white matter 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• leukoencephalopathy with vanishing white matter

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• ovarioleukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414.4. 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
	EIF2B1	NM_001414.4	MANE Select	c.*464A>C		3_prime_UTR	Exon 9 of 9	NP_001405.1	Q14232-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B1	ENST00000424014.7	TSL:1 MANE Select	c.*464A>C		3_prime_UTR	Exon 9 of 9	ENSP00000416250.2	Q14232-1
	EIF2B1	ENST00000929734.1		c.*464A>C		3_prime_UTR	Exon 10 of 10	ENSP00000599793.1
	EIF2B1	ENST00000857210.1		c.*464A>C		3_prime_UTR	Exon 10 of 10	ENSP00000527269.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 103710 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54864

African (AFR) AF: 0.00 AC: 0 AN: 2884

American (AMR) AF: 0.00 AC: 0 AN: 4454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2464

East Asian (EAS) AF: 0.00 AC: 0 AN: 4790

South Asian (SAS) AF: 0.00 AC: 0 AN: 16662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 388

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61382

Other (OTH) AF: 0.00 AC: 0 AN: 5330

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 3913

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.047
DANN	Benign	0.55
PhyloP100		-1.6

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: rs9919; hg19: chr12-124105839;