1-10371271-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

pheochromocytoma
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease type 2A1
Inheritance: AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
neuroblastoma, susceptibility to, 1
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KIF1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 291583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3 link	c.4946+9C>T	intron_variant	Intron 45 of 48	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1 link	c.4946+9C>T	intron_variant	Intron 45 of 48		NP_001352881.1
KIF1B	NM_015074.3 link	c.4808+9C>T	intron_variant	Intron 43 of 46		NP_055889.2	O60333-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1 link	c.4946+9C>T		intron_variant	Intron 45 of 48		NM_001365951.3	ENSP00000502065.1		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

GnomAD2 exomes

AF:

0.0335

AC:

8417

AN:

251330

AF XY:

0.0324

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 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

African (AFR)

AF:

0.0505

AC:

1690

AN:

33474

American (AMR)

AF:

0.0306

AC:

1366

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

1217

AN:

26134

East Asian (EAS)

AF:

0.0884

AC:

3510

AN:

39692

South Asian (SAS)

AF:

0.0258

AC:

2229

AN:

86236

European-Finnish (FIN)

AF:

0.0464

AC:

2477

AN:

53404

Middle Eastern (MID)

AF:

0.0832

AC:

479

AN:

5760

European-Non Finnish (NFE)

AF:

0.0203

AC:

22599

AN:

1111802

Other (OTH)

AF:

0.0342

AC:

2067

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1872

3743

5615

7486

9358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0355

AC:

5408

AN:

152236

Hom.:

116

Cov.:

AF XY:

0.0364

AC XY:

2711

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0480

AC:

1995

AN:

41544

American (AMR)

AF:

0.0322

AC:

493

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

181

AN:

3472

East Asian (EAS)

AF:

0.0817

AC:

422

AN:

5166

South Asian (SAS)

AF:

0.0267

AC:

129

AN:

4828

European-Finnish (FIN)

AF:

0.0502

AC:

532

AN:

10606

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0219

AC:

1492

AN:

68018

Other (OTH)

AF:

0.0417

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

270

540

810

1080

1350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

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. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Neuroblastoma

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.80

CADD

Benign

8.3

(source)

DANN

Benign

0.55

PhyloP100

0.0090

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over