3-184135231-T-C
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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
NR_183718.1 non_coding_transcript_exon
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.05
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]
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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-DT | NR_183718.1 | n.31A>G | non_coding_transcript_exon_variant | 1/3 | |||
EIF2B5-DT | NR_183719.1 | n.31A>G | non_coding_transcript_exon_variant | 1/4 | |||
EIF2B5-DT | NR_183720.1 | n.31A>G | non_coding_transcript_exon_variant | 1/3 | |||
EIF2B5-DT | NR_183721.1 | n.31A>G | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2B5-DT | ENST00000608135.1 | n.8A>G | non_coding_transcript_exon_variant | 1/3 | 5 | ||||
EIF2B5 | ENST00000491144.5 | n.194T>C | non_coding_transcript_exon_variant | 1/15 | 2 | ||||
EIF2B5-DT | ENST00000608232.5 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152212Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000911 AC: 90AN: 987452Hom.: 0 Cov.: 13 AF XY: 0.000121 AC XY: 60AN XY: 496426
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74366
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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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at