rs373520608
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The ENST00000347454.9(EIF2B4):c.930G>A(p.Glu310=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000122 in 1,614,206 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 3 hom. )
Consequence
EIF2B4
ENST00000347454.9 synonymous
ENST00000347454.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.52
Genes affected
EIF2B4 (HGNC:3260): (eukaryotic translation initiation factor 2B subunit delta) Eukaryotic initiation factor 2B (EIF2B), which is necessary for protein synthesis, is a GTP exchange factor composed of five different subunits. The protein encoded by this gene is the fourth, or delta, subunit. Defects in this gene are a cause of leukoencephalopathy with vanishing white matter (VWM) and ovarioleukodystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 2-27367157-C-T is Benign according to our data. Variant chr2-27367157-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000722 (11/152318) while in subpopulation SAS AF= 0.00186 (9/4826). AF 95% confidence interval is 0.000972. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EIF2B4 | NM_001034116.2 | c.930G>A | p.Glu310= | synonymous_variant | 10/13 | ENST00000347454.9 | NP_001029288.1 | |
GTF3C2-AS2 | NR_183825.1 | n.1746-267C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EIF2B4 | ENST00000347454.9 | c.930G>A | p.Glu310= | synonymous_variant | 10/13 | 1 | NM_001034116.2 | ENSP00000233552 | P4 | |
GTF3C2-AS2 | ENST00000412749.1 | n.201-267C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000251 AC: 63AN: 251490Hom.: 1 AF XY: 0.000368 AC XY: 50AN XY: 135920
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GnomAD4 exome AF: 0.000127 AC: 186AN: 1461888Hom.: 3 Cov.: 34 AF XY: 0.000194 AC XY: 141AN XY: 727246
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GnomAD4 genome AF: 0.0000722 AC: 11AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at