chr3-184135183-C-A

Variant names:

• chr3-184135183-C-A
• rs886058211
• ENST00000491144.5:n.146C>A

Variant summary

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

The ENST00000491144.5(EIF2B5):​n.146C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 528,158 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: EIF2B5 ENST00000491144.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.60
• Publications: 0 publications found

Genes affected

EIF2B5 (HGNC:3261): (eukaryotic translation initiation factor 2B subunit epsilon) 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, Nov 2009]

EIF2B5-DT (HGNC:55202): (EIF2B5 divergent transcript)

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=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491144.5. 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
	EIF2B5-DT	NR_183720.1		n.79G>T		non_coding_transcript_exon	Exon 1 of 3
	EIF2B5-DT	NR_183721.1		n.79G>T		non_coding_transcript_exon	Exon 1 of 2
	EIF2B5-DT	NR_183718.1		n.67+12G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B5	ENST00000491144.5	TSL:2	n.146C>A		non_coding_transcript_exon	Exon 1 of 15
	EIF2B5-DT	ENST00000608232.6	TSL:5	n.107G>T		non_coding_transcript_exon	Exon 1 of 3
	EIF2B5-DT	ENST00000609288.2	TSL:6	n.197G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000568 AC: 3 AN: 528158 Hom.: 0 Cov.: 6 AF XY: 0.00000362 AC XY: 1 AN XY: 276624

African (AFR) AF: 0.00 AC: 0 AN: 14040

American (AMR) AF: 0.00 AC: 0 AN: 21870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14690

East Asian (EAS) AF: 0.00 AC: 0 AN: 31328

South Asian (SAS) AF: 0.00 AC: 0 AN: 50288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2294

European-Non Finnish (NFE) AF: 0.00000600 AC: 2 AN: 333496

Other (OTH) AF: 0.0000350 AC: 1 AN: 28606

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	-0.77
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-1.6
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs886058211; hg19: chr3-183852971;