Variant chr3-184135283-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The ENST00000491144.5(EIF2B5):n.246C>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 0.0236 in 1,483,838 control chromosomes in the GnomAD database, including 499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.018 ( 42 hom., cov: 33)

Exomes 𝑓: 0.024 ( 457 hom. )

Consequence

EIF2B5
ENST00000491144.5 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.225

Variant links:

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 links:

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

EIF2B5-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0183 (2781/152364) while in subpopulation NFE AF= 0.0263 (1791/68050). AF 95% confidence interval is 0.0253. There are 42 homozygotes in gnomad4. There are 1283 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	Effect
EIF2B5-DT	NR_183718.1 linkuse as main transcript	upstream_gene_variant
EIF2B5-DT	NR_183719.1 linkuse as main transcript	upstream_gene_variant
EIF2B5-DT	NR_183720.1 linkuse as main transcript	upstream_gene_variant
EIF2B5-DT	NR_183721.1 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2B5	ENST00000491144.5 linkuse as main transcript	n.246C>G		non_coding_transcript_exon_variant	1/15	2
EIF2B5-DT	ENST00000608135.1 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2782

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00569

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0273

GnomAD4 exome

AF:

0.0243

AC:

32297

AN:

1331474

Hom.:

457

Cov.:

AF XY:

0.0244

AC XY:

16084

AN XY:

659334

show subpopulations

Gnomad4 AFR exome

AF:

0.00542

Gnomad4 AMR exome

AF:

0.0147

Gnomad4 ASJ exome

AF:

0.0579

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0183

AC:

2781

AN:

152364

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1283

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00565

Gnomad4 AMR

AF:

0.0197

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.00791

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0205

Hom.:

Bravo

AF:

0.0189

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vanishing white matter disease

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.4

DANN

Benign

0.77

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over