3-184146025-A-T

Position:

• chr3-184146025-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B5	ENST00000468748.7	n.4323A>T		non_coding_transcript_exon_variant	13/13	4

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

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.312

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs844540; hg19: chr3-183863813;