3-184135231-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NR_183718.1(EIF2B5-DT):​n.31A>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 0.0000851 in 1,139,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

EIF2B5-DT
NR_183718.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05
Variant links:
Genes affected
EIF2B5-DT (HGNC:55202): (EIF2B5 divergent transcript)
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EIF2B5-DTNR_183718.1 linkuse as main transcriptn.31A>G non_coding_transcript_exon_variant 1/3
EIF2B5-DTNR_183719.1 linkuse as main transcriptn.31A>G non_coding_transcript_exon_variant 1/4
EIF2B5-DTNR_183720.1 linkuse as main transcriptn.31A>G non_coding_transcript_exon_variant 1/3
EIF2B5-DTNR_183721.1 linkuse as main transcriptn.31A>G non_coding_transcript_exon_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF2B5-DTENST00000608135.1 linkuse as main transcriptn.8A>G non_coding_transcript_exon_variant 1/35
EIF2B5ENST00000491144.5 linkuse as main transcriptn.194T>C non_coding_transcript_exon_variant 1/152
EIF2B5-DTENST00000608232.5 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000911
AC:
90
AN:
987452
Hom.:
0
Cov.:
13
AF XY:
0.000121
AC XY:
60
AN XY:
496426
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000111
Gnomad4 OTH exome
AF:
0.0000680
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000827
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
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
-0.82
CADD
Benign
4.1
DANN
Benign
0.30

Splicing

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: rs369493689; hg19: chr3-183853019; API