3-184146025-A-T

Variant names:

• chr3-184146025-A-T
• rs844540
• ENST00000468748.7:n.4323A>T

Variant summary

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

The ENST00000468748.7(EIF2B5):​n.4323A>T 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 0.309 in 152,100 control chromosomes in the GnomAD database, including 7,609 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 (7609 hom., cov: 33)
• Consequence: EIF2B5 ENST00000468748.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000468748.7. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B5	ENST00000468748.7	TSL:4	n.4323A>T		non_coding_transcript_exon	Exon 13 of 13
	EIF2B5-DT	ENST00000723636.1		n.61-5070T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46906 AN: 151980 Hom.: 7592 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.309 AC: 46948 AN: 152100 Hom.: 7609 Cov.: 33 AF XY: 0.313 AC XY: 23300 AN XY: 74382

African (AFR) AF: 0.234 AC: 9697 AN: 41504

American (AMR) AF: 0.339 AC: 5177 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 959 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2782 AN: 5172

South Asian (SAS) AF: 0.413 AC: 1993 AN: 4826

European-Finnish (FIN) AF: 0.306 AC: 3237 AN: 10562

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22030 AN: 67966

Other (OTH) AF: 0.312 AC: 660 AN: 2114

Alfa AF: 0.320 Hom.: 969

Bravo AF: 0.306

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.66
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs844540; hg19: chr3-183863813;