rs72867431

Positions:

chr1-10371271-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.4946+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,613,834 control chromosomes in the GnomAD database, including 781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 116 hom., cov: 31)

Exomes 𝑓: 0.026 ( 665 hom. )

Consequence

KIF1B
NM_001365951.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.00900

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=-0.8).

BP6

Variant 1-10371271-C-T is Benign according to our data. Variant chr1-10371271-C-T is described in ClinVar as [Benign]. Clinvar id is 291583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-10371271-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KIF1B	NM_001365951.3 linkuse as main transcript	c.4946+9C>T	intron_variant	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1 linkuse as main transcript	c.4946+9C>T	intron_variant		NP_001352881.1
KIF1B	NM_015074.3 linkuse as main transcript	c.4808+9C>T	intron_variant		NP_055889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1 linkuse as main transcript	c.4946+9C>T		intron_variant			NM_001365951.3	ENSP00000502065	P1	O60333-1

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5402

AN:

152118

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0481

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0323

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.0811

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0335

AC:

8417

AN:

251330

Hom.:

167

AF XY:

0.0324

AC XY:

4406

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0495

Gnomad AMR exome

AF:

0.0294

Gnomad ASJ exome

AF:

0.0466

Gnomad EAS exome

AF:

0.0823

Gnomad SAS exome

AF:

0.0242

Gnomad FIN exome

AF:

0.0464

Gnomad NFE exome

AF:

0.0232

Gnomad OTH exome

AF:

0.0375

GnomAD4 exome

AF:

0.0257

AC:

37634

AN:

1461598

Hom.:

665

Cov.:

AF XY:

0.0257

AC XY:

18658

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0505

Gnomad4 AMR exome

AF:

0.0306

Gnomad4 ASJ exome

AF:

0.0466

Gnomad4 EAS exome

AF:

0.0884

Gnomad4 SAS exome

AF:

0.0258

Gnomad4 FIN exome

AF:

0.0464

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0342

GnomAD4 genome

AF:

0.0355

AC:

5408

AN:

152236

Hom.:

116

Cov.:

AF XY:

0.0364

AC XY:

2711

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0480

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.0817

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.0502

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0417

Alfa

AF:

0.0296

Hom.:

Bravo

AF:

0.0358

Asia WGS

AF:

0.0630

AC:

220

AN:

3478

ClinVar

Significance: 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	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, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

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

- -

Neuroblastoma

Benign:1

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. -

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

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

DANN

Benign

0.55

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