rs139613776
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001365951.3(KIF1B):c.608+8dup variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,613,808 control chromosomes in the GnomAD database, including 576 homozygotes. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.019 ( 41 hom., cov: 32)
Exomes 𝑓: 0.024 ( 535 hom. )
Consequence
KIF1B
NM_001365951.3 splice_region, intron
NM_001365951.3 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.15
Genes affected
KIF1B (HGNC:16636): (kinesin family member 1B) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in chemical synaptic transmission; dense core granule cytoskeletal transport; and vesicle-mediated transport. Predicted to act upstream of or within mitochondrion transport along microtubule. Predicted to be located in cytoplasmic vesicle membrane and neuron projection. Predicted to be part of kinesin complex. Predicted to be active in several cellular components, including axon; dendrite; and microtubule. Implicated in Charcot-Marie-Tooth disease type 2A1; carcinoma (multiple); multiple sclerosis; neuroblastoma; and pheochromocytoma. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 1-10267565-T-TA is Benign according to our data. Variant chr1-10267565-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 220468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0187 (2854/152272) while in subpopulation NFE AF= 0.0279 (1898/68024). AF 95% confidence interval is 0.0269. There are 41 homozygotes in gnomad4. There are 1425 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2854 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF1B | NM_001365951.3 | c.608+8dup | splice_region_variant, intron_variant | ENST00000676179.1 | NP_001352880.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF1B | ENST00000676179.1 | c.608+8dup | splice_region_variant, intron_variant | NM_001365951.3 | ENSP00000502065 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0188 AC: 2854AN: 152154Hom.: 41 Cov.: 32
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GnomAD3 exomes AF: 0.0184 AC: 4615AN: 251268Hom.: 78 AF XY: 0.0181 AC XY: 2460AN XY: 135806
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GnomAD4 exome AF: 0.0240 AC: 35066AN: 1461536Hom.: 535 Cov.: 32 AF XY: 0.0235 AC XY: 17069AN XY: 727074
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GnomAD4 genome AF: 0.0187 AC: 2854AN: 152272Hom.: 41 Cov.: 32 AF XY: 0.0191 AC XY: 1425AN XY: 74440
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The KIF1B c.608+8dupA variant was not identified in the literature nor was it identified in the Cosmic database. The variant was identified in dbSNP (ID: rs139613776), ClinVar (classified as benign by Invitae and Prevention Genetics in 2017, likely benign by Illumina in 2016) and LOVD 3.0. The variant was identified in control databases in 5227 of 282654 chromosomes (87 homozygous) at a frequency of 0.018493 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (Finnish) in 1053 of 25122 chromosomes (freq: 0.04192), European (non-Finnish) in 3413 of 129024 chromosomes (freq: 0.02645), Other in 155 of 7216 chromosomes (freq: 0.02148), Latino in 346 of 35434 chromosomes (freq: 0.009765), Ashkenazi Jewish in 70 of 10360 chromosomes (freq: 0.006757), African in 102 of 24956 chromosomes (freq: 0.004087), South Asian in 87 of 30614 chromosomes (freq: 0.002842), and East Asian in 1 of 19928 chromosomes (freq: 0.00005). The variant occurs outside of the splicing consensus sequence however 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE) predict the creation of a new 5' splice site; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Charcot-Marie-Tooth disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Neuroblastoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Charcot-Marie-Tooth disease type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
KIF1B-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 09, 2024 | 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). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at