chr2-27369556-C-T
Variant summary
Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_001034116.2(EIF2B4):c.76-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,613,406 control chromosomes in the GnomAD database, including 125,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001034116.2 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- leukoencephalopathy with vanishing white matter 4Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
- leukoencephalopathy with vanishing white matterInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- leukoencephalopathy with vanishing white matter 1Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- ovarioleukodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.408 AC: 61985AN: 151866Hom.: 13131 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.398 AC: 100015AN: 251384 AF XY: 0.391 show subpopulations
GnomAD4 exome AF: 0.386 AC: 564162AN: 1461422Hom.: 111864 Cov.: 47 AF XY: 0.385 AC XY: 279597AN XY: 727030 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.408 AC: 62074AN: 151984Hom.: 13164 Cov.: 32 AF XY: 0.408 AC XY: 30333AN XY: 74304 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:4
This variant is associated with the following publications: (PMID: 28008009) -
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not specified Benign:2
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Vanishing white matter disease Benign:2
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at