chr3-184135269-C-T
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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
ENST00000491144.5 non_coding_transcript_exon
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.459
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]
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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-DT | NR_183718.1 | upstream_gene_variant | |||||
EIF2B5-DT | NR_183719.1 | upstream_gene_variant | |||||
EIF2B5-DT | NR_183720.1 | upstream_gene_variant | |||||
EIF2B5-DT | NR_183721.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2B5 | ENST00000491144.5 | n.232C>T | non_coding_transcript_exon_variant | 1/15 | 2 | ||||
EIF2B5-DT | ENST00000608135.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00167 AC: 254AN: 152254Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00234 AC: 2991AN: 1279560Hom.: 2 Cov.: 20 AF XY: 0.00234 AC XY: 1490AN XY: 635736
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GnomAD4 genome AF: 0.00167 AC: 254AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.00148 AC XY: 110AN XY: 74516
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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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at