chr1-10295776-C-T

Position:

chr1-10295776-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.1777+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,603,204 control chromosomes in the GnomAD database, including 68,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5595 hom., cov: 31)

Exomes 𝑓: 0.29 ( 62856 hom. )

Consequence

KIF1B
NM_001365951.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.262

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-10295776-C-T is Benign according to our data. Variant chr1-10295776-C-T is described in ClinVar as [Benign]. Clinvar id is 177960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-10295776-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1B	NM_001365951.3 linkuse as main transcript	c.1777+10C>T		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.1777+10C>T		intron_variant			NM_001365951.3	ENSP00000502065.1		O60333-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40398

AN:

151908

Hom.:

5574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.284

AC:

71355

AN:

250910

Hom.:

10438

AF XY:

0.281

AC XY:

38082

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.350

Gnomad ASJ exome

AF:

0.275

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:

0.293

AC:

424561

AN:

1451178

Hom.:

62856

Cov.:

AF XY:

0.291

AC XY:

210002

AN XY:

722420

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.289

GnomAD4 genome

AF:

0.266

AC:

40461

AN:

152026

Hom.:

5595

Cov.:

AF XY:

0.267

AC XY:

19805

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.276

Hom.:

1344

Bravo

AF:

0.267

Asia WGS

AF:

0.278

AC:

963

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 28, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 20, 2013	The 1639+10C_T variant in KIF1B: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, has been identified in 30% (2553/8600) of Euro pean American chromosomes and 26% (820/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs3 753037). -

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	-	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Pheochromocytoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Neuroblastoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Charcot-Marie-Tooth disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Charcot-Marie-Tooth disease type 2A1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.3

DANN

Benign

0.47

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.

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