chr3-184135269-C-T

Variant summary

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

The ENST00000491144.5(EIF2B5):​n.232C>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 0.00227 in 1,431,932 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 2 hom. )

Consequence

EIF2B5
ENST00000491144.5 non_coding_transcript_exon

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.459
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-DT (HGNC:55202): (EIF2B5 divergent transcript)

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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=-0.7).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00167 (254/152372) while in subpopulation NFE AF= 0.00306 (208/68038). AF 95% confidence interval is 0.00272. There are 0 homozygotes in gnomad4. There are 110 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 GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EIF2B5-DTNR_183718.1 linkuse as main transcript upstream_gene_variant
EIF2B5-DTNR_183719.1 linkuse as main transcript upstream_gene_variant
EIF2B5-DTNR_183720.1 linkuse as main transcript upstream_gene_variant
EIF2B5-DTNR_183721.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF2B5ENST00000491144.5 linkuse as main transcriptn.232C>T non_coding_transcript_exon_variant 1/152
EIF2B5-DTENST00000608135.1 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00167
AC:
254
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000386
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00113
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00306
Gnomad OTH
AF:
0.00143
GnomAD4 exome
AF:
0.00234
AC:
2991
AN:
1279560
Hom.:
2
Cov.:
20
AF XY:
0.00234
AC XY:
1490
AN XY:
635736
show subpopulations
Gnomad4 AFR exome
AF:
0.000240
Gnomad4 AMR exome
AF:
0.000543
Gnomad4 ASJ exome
AF:
0.000166
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000185
Gnomad4 FIN exome
AF:
0.00142
Gnomad4 NFE exome
AF:
0.00287
Gnomad4 OTH exome
AF:
0.00154
GnomAD4 genome
AF:
0.00167
AC:
254
AN:
152372
Hom.:
0
Cov.:
33
AF XY:
0.00148
AC XY:
110
AN XY:
74516
show subpopulations
Gnomad4 AFR
AF:
0.000385
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00113
Gnomad4 NFE
AF:
0.00306
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00196
Hom.:
0
Bravo
AF:
0.00143
Asia WGS
AF:
0.000289
AC:
1
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 submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
5.2
DANN
Benign
0.90

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.

Other links and lift over

dbSNP: rs182550783; hg19: chr3-183853057; API