rs41274456

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001365951.3(KIF1B):c.1180+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,611,316 control chromosomes in the GnomAD database, including 1,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 108 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1227 hom. )

Consequence

KIF1B
NM_001365951.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.65

Publications

4 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=-0.82).

BP6

Variant 1-10278146-C-T is Benign according to our data. Variant chr1-10278146-C-T is described in ClinVar as Benign. ClinVar VariationId is 260540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0303 (4613/152190) while in subpopulation NFE AF = 0.0454 (3084/67988). AF 95% confidence interval is 0.044. There are 108 homozygotes in GnomAd4. There are 2226 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4613 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3 link	c.1180+18C>T		intron_variant	Intron 13 of 48	ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1 link	c.1180+18C>T		intron_variant	Intron 13 of 48		NM_001365951.3	ENSP00000502065.1		O60333-1

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4614

AN:

152072

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00640

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.0619

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0152

Gnomad FIN

AF:

0.0584

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0454

Gnomad OTH

AF:

0.0254

GnomAD2 exomes

AF:

0.0326

AC:

8184

AN:

251288

AF XY:

0.0328

show subpopulations

Gnomad AFR exome

AF:

0.00628

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0610

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0585

Gnomad NFE exome

AF:

0.0439

Gnomad OTH exome

AF:

0.0391

GnomAD4 exome

AF:

0.0386

AC:

56372

AN:

1459126

Hom.:

1227

Cov.:

AF XY:

0.0383

AC XY:

27801

AN XY:

726036

show subpopulations

African (AFR)

AF:

0.00634

AC:

212

AN:

33422

American (AMR)

AF:

0.0154

AC:

687

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0597

AC:

1559

AN:

26104

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39638

South Asian (SAS)

AF:

0.0163

AC:

1404

AN:

86138

European-Finnish (FIN)

AF:

0.0558

AC:

2976

AN:

53358

Middle Eastern (MID)

AF:

0.0189

AC:

109

AN:

5764

European-Non Finnish (NFE)

AF:

0.0426

AC:

47308

AN:

1109716

Other (OTH)

AF:

0.0351

AC:

2115

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2309

4619

6928

9238

11547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1688

3376

5064

6752

8440

<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:

0.0303

AC:

4613

AN:

152190

Hom.:

108

Cov.:

AF XY:

0.0299

AC XY:

2226

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00638

AC:

265

AN:

41550

American (AMR)

AF:

0.0158

AC:

242

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0619

AC:

215

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0152

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0584

AC:

618

AN:

10580

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0454

AC:

3084

AN:

67988

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

234

468

702

936

1170

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:

0.0406

Hom.:

Bravo

AF:

0.0270

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

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

-0.82

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

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