1-10268280-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365951.3(KIF1B):​c.720+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,493,890 control chromosomes in the GnomAD database, including 63,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5373 hom., cov: 31)
Exomes 𝑓: 0.29 ( 58038 hom. )

Consequence

KIF1B
NM_001365951.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.56
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 1-10268280-C-T is Benign according to our data. Variant chr1-10268280-C-T is described in ClinVar as [Benign]. Clinvar id is 260542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-10268280-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF1BNM_001365951.3 linkc.720+17C>T intron_variant Intron 7 of 48 ENST00000676179.1 NP_001352880.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF1BENST00000676179.1 linkc.720+17C>T intron_variant Intron 7 of 48 NM_001365951.3 ENSP00000502065.1 O60333-1

Frequencies

GnomAD3 genomes
AF:
0.257
AC:
38990
AN:
151908
Hom.:
5356
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.158
Gnomad AMI
AF:
0.363
Gnomad AMR
AF:
0.320
Gnomad ASJ
AF:
0.266
Gnomad EAS
AF:
0.285
Gnomad SAS
AF:
0.240
Gnomad FIN
AF:
0.293
Gnomad MID
AF:
0.206
Gnomad NFE
AF:
0.294
Gnomad OTH
AF:
0.267
GnomAD3 exomes
AF:
0.282
AC:
70135
AN:
248986
Hom.:
10137
AF XY:
0.279
AC XY:
37491
AN XY:
134552
show subpopulations
Gnomad AFR exome
AF:
0.153
Gnomad AMR exome
AF:
0.349
Gnomad ASJ exome
AF:
0.270
Gnomad EAS exome
AF:
0.291
Gnomad SAS exome
AF:
0.230
Gnomad FIN exome
AF:
0.293
Gnomad NFE exome
AF:
0.292
Gnomad OTH exome
AF:
0.269
GnomAD4 exome
AF:
0.292
AC:
391352
AN:
1341862
Hom.:
58038
Cov.:
20
AF XY:
0.290
AC XY:
195281
AN XY:
673870
show subpopulations
Gnomad4 AFR exome
AF:
0.149
Gnomad4 AMR exome
AF:
0.341
Gnomad4 ASJ exome
AF:
0.272
Gnomad4 EAS exome
AF:
0.256
Gnomad4 SAS exome
AF:
0.226
Gnomad4 FIN exome
AF:
0.301
Gnomad4 NFE exome
AF:
0.302
Gnomad4 OTH exome
AF:
0.285
GnomAD4 genome
AF:
0.257
AC:
39040
AN:
152028
Hom.:
5373
Cov.:
31
AF XY:
0.258
AC XY:
19141
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.158
Gnomad4 AMR
AF:
0.321
Gnomad4 ASJ
AF:
0.266
Gnomad4 EAS
AF:
0.285
Gnomad4 SAS
AF:
0.240
Gnomad4 FIN
AF:
0.293
Gnomad4 NFE
AF:
0.294
Gnomad4 OTH
AF:
0.272
Alfa
AF:
0.242
Hom.:
1521
Bravo
AF:
0.257
Asia WGS
AF:
0.275
AC:
955
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Jul 28, 2020
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease Benign:1
-
Molecular Genetics Laboratory, London Health Sciences Centre
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Pheochromocytoma Benign:1
Aug 19, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 2 Benign:1
Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 2A1 Benign:1
Aug 19, 2021
Genome-Nilou Lab
Significance: 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
-0.83
CADD
Benign
3.5
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs1339458; hg19: chr1-10328338; COSMIC: COSV55802811; API