rs17034660

Positions:

chr1-10282464-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001365951.3(KIF1B):c.1365G>A(p.Thr455=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,006 control chromosomes in the GnomAD database, including 760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 113 hom., cov: 32)

Exomes 𝑓: 0.026 ( 647 hom. )

Consequence

KIF1B
NM_001365951.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.468

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 1-10282464-G-A is Benign according to our data. Variant chr1-10282464-G-A is described in ClinVar as [Benign]. Clinvar id is 291522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-10282464-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.468 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0677 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.1365G>A	p.Thr455=	synonymous_variant	15/49	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.1365G>A	p.Thr455=	synonymous_variant	15/49		NM_001365951.3	ENSP00000502065	P1	O60333-1

Frequencies

GnomAD3 genomes

AF:

0.0351

AC:

5344

AN:

152098

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0481

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0314

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.0733

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0330

AC:

8292

AN:

251286

Hom.:

155

AF XY:

0.0320

AC XY:

4339

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0497

Gnomad AMR exome

AF:

0.0295

Gnomad ASJ exome

AF:

0.0464

Gnomad EAS exome

AF:

0.0750

Gnomad SAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.0464

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0372

GnomAD4 exome

AF:

0.0256

AC:

37434

AN:

1461790

Hom.:

647

Cov.:

AF XY:

0.0255

AC XY:

18539

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0507

Gnomad4 AMR exome

AF:

0.0305

Gnomad4 ASJ exome

AF:

0.0464

Gnomad4 EAS exome

AF:

0.0836

Gnomad4 SAS exome

AF:

0.0257

Gnomad4 FIN exome

AF:

0.0464

Gnomad4 NFE exome

AF:

0.0204

Gnomad4 OTH exome

AF:

0.0335

GnomAD4 genome

AF:

0.0351

AC:

5349

AN:

152216

Hom.:

113

Cov.:

AF XY:

0.0361

AC XY:

2683

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0481

Gnomad4 AMR

AF:

0.0313

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.0738

Gnomad4 SAS

AF:

0.0268

Gnomad4 FIN

AF:

0.0502

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0271

Hom.:

Bravo

AF:

0.0353

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

EpiCase

AF:

0.0264

EpiControl

AF:

0.0228

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	-	- -

not specified

Benign:1

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. -

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

-0.39

CADD

Benign

7.5

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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