chr20-58445517-A-G
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1
The NM_004738.5(VAPB):c.*1282A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 454,294 control chromosomes in the GnomAD database, including 7,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.16 ( 2090 hom., cov: 32)
Exomes 𝑓: 0.17 ( 5060 hom. )
Consequence
VAPB
NM_004738.5 3_prime_UTR
NM_004738.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.47
Genes affected
VAPB (HGNC:12649): (VAMP associated protein B and C) The protein encoded by this gene is a type IV membrane protein found in plasma and intracellular vesicle membranes. The encoded protein is found as a homodimer and as a heterodimer with VAPA. This protein also can interact with VAMP1 and VAMP2 and may be involved in vesicle trafficking. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 20-58445517-A-G is Benign according to our data. Variant chr20-58445517-A-G is described in ClinVar as [Benign]. Clinvar id is 338947.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VAPB | NM_004738.5 | c.*1282A>G | 3_prime_UTR_variant | 6/6 | ENST00000475243.6 | ||
VAPB | NM_001195677.2 | c.*1352A>G | 3_prime_UTR_variant | 3/3 | |||
VAPB | NR_036633.2 | n.2060A>G | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VAPB | ENST00000475243.6 | c.*1282A>G | 3_prime_UTR_variant | 6/6 | 1 | NM_004738.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.158 AC: 23973AN: 152026Hom.: 2086 Cov.: 32
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GnomAD3 exomes AF: 0.163 AC: 22236AN: 136630Hom.: 2299 AF XY: 0.171 AC XY: 12719AN XY: 74180
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GnomAD4 exome AF: 0.168 AC: 50753AN: 302152Hom.: 5060 Cov.: 0 AF XY: 0.179 AC XY: 30767AN XY: 172210
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GnomAD4 genome AF: 0.158 AC: 23983AN: 152142Hom.: 2090 Cov.: 32 AF XY: 0.166 AC XY: 12326AN XY: 74356
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Amyotrophic lateral sclerosis type 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Adult-onset proximal spinal muscular atrophy, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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