rs886038609

Positions:

chr1-10258485-CTT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001365951.3(KIF1B):c.184-6_184-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,613,084 control chromosomes in the GnomAD database, including 565 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 40 hom., cov: 32)

Exomes 𝑓: 0.024 ( 525 hom. )

Consequence

KIF1B
NM_001365951.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.16

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]

KIF1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-10258485-CTT-C is Benign according to our data. Variant chr1-10258485-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 260541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-10258485-CTT-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0187 (2851/152234) while in subpopulation NFE AF= 0.0279 (1897/67990). AF 95% confidence interval is 0.0269. There are 40 homozygotes in gnomad4. There are 1418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2851 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1B	NM_001365951.3 linkuse as main transcript	c.184-6_184-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1 linkuse as main transcript	c.184-6_184-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001365951.3	ENSP00000502065	P1	O60333-1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2851

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00461

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0443

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0183

AC:

4593

AN:

251318

Hom.:

AF XY:

0.0180

AC XY:

2449

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.00969

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00284

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0263

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0237

AC:

34668

AN:

1460850

Hom.:

525

AF XY:

0.0232

AC XY:

16887

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.00937

Gnomad4 ASJ exome

AF:

0.00658

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00220

Gnomad4 FIN exome

AF:

0.0404

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0187

AC:

2851

AN:

152234

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1418

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00460

Gnomad4 AMR

AF:

0.0141

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0443

Gnomad4 NFE

AF:

0.0279

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0200

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0222

EpiControl

AF:

0.0244

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 13, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jun 24, 2020	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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