3-184135231-T-G

Variant names:

• chr3-184135231-T-G
• rs369493689
• ENST00000491144.5:n.194T>G

Variant summary

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

The ENST00000491144.5(EIF2B5):​n.194T>G 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 0.00000203 in 987,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: EIF2B5 ENST00000491144.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-0.81).

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_183718.1		n.31A>C		non_coding_transcript_exon	Exon 1 of 3
	EIF2B5-DT	NR_183719.1		n.31A>C		non_coding_transcript_exon	Exon 1 of 4
	EIF2B5-DT	NR_183720.1		n.31A>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B5	ENST00000491144.5	TSL:2	n.194T>G		non_coding_transcript_exon	Exon 1 of 15
	EIF2B5-DT	ENST00000608135.2	TSL:5	n.187A>C		non_coding_transcript_exon	Exon 1 of 3
	EIF2B5-DT	ENST00000608232.6	TSL:5	n.59A>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000203 AC: 2 AN: 987452 Hom.: 0 Cov.: 13 AF XY: 0.00000403 AC XY: 2 AN XY: 496426

African (AFR) AF: 0.00 AC: 0 AN: 23702

American (AMR) AF: 0.00 AC: 0 AN: 31530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20058

East Asian (EAS) AF: 0.00 AC: 0 AN: 33660

South Asian (SAS) AF: 0.00 AC: 0 AN: 64856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4432

European-Non Finnish (NFE) AF: 0.00000276 AC: 2 AN: 723696

Other (OTH) AF: 0.00 AC: 0 AN: 44124

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.28
PhyloP100		-1.0
PromoterAI		-0.13	Neutral

Splicing

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

Other links and lift over

dbSNP: rs369493689; hg19: chr3-183853019;