rs117815481

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001244008.2(KIF1A):c.4744-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,611,786 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

KIF1A
NM_001244008.2 splice_region, intron

Scores

Splicing: ADA: 0.00002356

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:5

Conservation

PhyloP100: -0.434

Variant links:

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]

KIF1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-240721043-G-A is Benign according to our data. Variant chr2-240721043-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 335259.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000309 (47/152338) while in subpopulation EAS AF= 0.00405 (21/5186). AF 95% confidence interval is 0.00271. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.4744-5C>T		splice_region_variant, intron_variant	Intron 44 of 48	ENST00000498729.9	NP_001230937.1	Q12756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9 link	c.4744-5C>T		splice_region_variant, intron_variant	Intron 44 of 48	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000360

AC:

AN:

244534

Hom.:

AF XY:

0.000360

AC XY:

AN XY:

133396

show subpopulations

Gnomad AFR exome

AF:

0.000199

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00297

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.000146

Gnomad NFE exome

AF:

0.000181

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000249

AC:

363

AN:

1459448

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

725912

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00222

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.0000958

Gnomad4 NFE exome

AF:

0.000208

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000309

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000242

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Jul 16, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 25, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Apr 27, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KIF1A: BP4, BP5, BS1 -

Hereditary spastic paraplegia 30

Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

KIF1A-related disorder

Benign:1

Nov 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neuropathy, hereditary sensory, type 2C;C5235139:Hereditary spastic paraplegia 30;C5393830:Intellectual disability, autosomal dominant 9

Benign:1

Dec 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over