rs775481158
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_001365951.3(KIF1B):c.4850G>A(p.Arg1617Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1617W) has been classified as Likely benign.
Frequency
Consequence
NM_001365951.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF1B | NM_001365951.3 | c.4850G>A | p.Arg1617Gln | missense_variant | 45/49 | ENST00000676179.1 | |
KIF1B | NM_001365952.1 | c.4850G>A | p.Arg1617Gln | missense_variant | 45/49 | ||
KIF1B | NM_015074.3 | c.4712G>A | p.Arg1571Gln | missense_variant | 43/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF1B | ENST00000676179.1 | c.4850G>A | p.Arg1617Gln | missense_variant | 45/49 | NM_001365951.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152040Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000385 AC XY: 28AN XY: 727238
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152040Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74230
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 29, 2023 | The p.R1571Q variant (also known as c.4712G>A), located in coding exon 42 of the KIF1B gene, results from a G to A substitution at nucleotide position 4712. The arginine at codon 1571 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1571 of the KIF1B protein (p.Arg1571Gln). This variant is present in population databases (rs775481158, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of KIF1B-related conditions (PMID: 34169998). ClinVar contains an entry for this variant (Variation ID: 575103). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at