rs77172218
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001365951.3(KIF1B):c.4798G>A(p.Val1600Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,613,930 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001365951.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1B | NM_001365951.3 | c.4798G>A | p.Val1600Met | missense_variant | 44/49 | ENST00000676179.1 | |
KIF1B | NM_001365952.1 | c.4798G>A | p.Val1600Met | missense_variant | 44/49 | ||
KIF1B | NM_015074.3 | c.4660G>A | p.Val1554Met | missense_variant | 42/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1B | ENST00000676179.1 | c.4798G>A | p.Val1600Met | missense_variant | 44/49 | NM_001365951.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0107 AC: 1630AN: 152174Hom.: 13 Cov.: 32
GnomAD3 exomes AF: 0.00994 AC: 2500AN: 251470Hom.: 26 AF XY: 0.0102 AC XY: 1393AN XY: 135910
GnomAD4 exome AF: 0.0146 AC: 21285AN: 1461638Hom.: 164 Cov.: 31 AF XY: 0.0143 AC XY: 10421AN XY: 727140
GnomAD4 genome ? AF: 0.0107 AC: 1631AN: 152292Hom.: 13 Cov.: 32 AF XY: 0.0102 AC XY: 757AN XY: 74480
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 28, 2020 | This alteration is classified as 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. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 30, 2023 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Charcot-Marie-Tooth disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Neuroblastoma 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. - |
Charcot-Marie-Tooth disease type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at