rs113994033
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001034116.2(EIF2B4):c.1070G>A(p.Arg357Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R357W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001034116.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF2B4 | NM_001034116.2 | c.1070G>A | p.Arg357Gln | missense_variant | 11/13 | ENST00000347454.9 | |
GTF3C2-AS2 | NR_183825.1 | n.1746-544C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2B4 | ENST00000347454.9 | c.1070G>A | p.Arg357Gln | missense_variant | 11/13 | 1 | NM_001034116.2 | P4 | |
GTF3C2-AS2 | ENST00000412749.1 | n.201-544C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251348Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461876Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 727234
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74448
ClinVar
Submissions by phenotype
Leukoencephalopathy with vanishing white matter 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2002 | - - |
Vanishing white matter disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Nov 28, 2018 | The EIF2B4 c.1067G>A (p.Arg356Gln) missense variant has been reported in three individuals, including a sibling pair, affected with white matter vanishing disease, all in a compound heterozygous state with a missense variant. The variant was present in one unaffected parent in a heterozygous state, absent from 120 control chromosomes and is reported at a frequency of 0.000012 in the Total population of the Genome Aggregation Database. Based on the limited evidence, the p.Arg356Gln variant is classified as a variant of unknown significance but suspicious for pathogenicity for childhood ataxia with central nervous system hypomyelination/vanishing white matter. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at