rs566283411
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_SupportingBP6BS2
The NM_004738.5(VAPB):c.479_481delCTT(p.Ser160del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0027 in 1,614,114 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004738.5 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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VAPB | NM_004738.5 | c.479_481delCTT | p.Ser160del | disruptive_inframe_deletion | Exon 5 of 6 | ENST00000475243.6 | NP_004729.1 | |
VAPB | NM_001195677.2 | c.212-3088_212-3086delCTT | intron_variant | Intron 2 of 2 | NP_001182606.1 | |||
VAPB | NR_036633.2 | n.525_527delCTT | non_coding_transcript_exon_variant | Exon 3 of 4 | ||||
VAPB | XR_001754433.3 | n.873_875delCTT | non_coding_transcript_exon_variant | Exon 6 of 6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00158 AC: 241AN: 152152Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00168 AC: 421AN: 251172Hom.: 1 AF XY: 0.00164 AC XY: 223AN XY: 135778
GnomAD4 exome AF: 0.00282 AC: 4117AN: 1461844Hom.: 11 AF XY: 0.00274 AC XY: 1994AN XY: 727222
GnomAD4 genome AF: 0.00158 AC: 241AN: 152270Hom.: 1 Cov.: 32 AF XY: 0.00146 AC XY: 109AN XY: 74438
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
This variant is associated with the following publications: (PMID: 21989245, 22878164, 19183264, 18322265, 23971766, 23446633) -
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VAPB: PM4:Supporting, BS1, BS2 -
not specified Benign:2
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
VAPB-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Amyotrophic Lateral Sclerosis, Dominant Benign:1
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Spinal Muscular Atrophy, Dominant Benign:1
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Amyotrophic lateral sclerosis type 8;C1854058:Adult-onset proximal spinal muscular atrophy, autosomal dominant Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at