rs56024577
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001244008.2(KIF1A):c.3641-8C>T variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.279 in 1,543,814 control chromosomes in the GnomAD database, including 66,318 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.24 ( 5486 hom., cov: 33)
Exomes 𝑓: 0.28 ( 60832 hom. )
Consequence
KIF1A
NM_001244008.2 splice_region, splice_polypyrimidine_tract, intron
NM_001244008.2 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0003042
2
Clinical Significance
Conservation
PhyloP100: 3.72
Genes affected
KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-240741385-G-A is Benign according to our data. Variant chr2-240741385-G-A is described in ClinVar as [Benign]. Clinvar id is 129391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240741385-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF1A | NM_001244008.2 | c.3641-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000498729.9 | NP_001230937.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF1A | ENST00000498729.9 | c.3641-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001244008.2 | ENSP00000438388 |
Frequencies
GnomAD3 genomes AF: 0.235 AC: 35771AN: 152008Hom.: 5473 Cov.: 33
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GnomAD3 exomes AF: 0.347 AC: 57808AN: 166444Hom.: 11293 AF XY: 0.352 AC XY: 31512AN XY: 89606
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GnomAD4 exome AF: 0.284 AC: 395390AN: 1391688Hom.: 60832 Cov.: 30 AF XY: 0.291 AC XY: 199666AN XY: 686874
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GnomAD4 genome AF: 0.235 AC: 35797AN: 152126Hom.: 5486 Cov.: 33 AF XY: 0.247 AC XY: 18348AN XY: 74372
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ClinVar
Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Hereditary spastic paraplegia 30 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
Neuropathy, hereditary sensory, type 2C Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Intellectual disability, autosomal dominant 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at