NM_001365951.3:c.*1159G>A

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.*1159G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 185,554 control chromosomes in the GnomAD database, including 1,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 948 hom., cov: 32)

Exomes 𝑓: 0.11 ( 234 hom. )

Consequence

KIF1B
NM_001365951.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.952

Publications

5 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=-0.85).

BP6

Variant 1-10377746-G-A is Benign according to our data. Variant chr1-10377746-G-A is described in ClinVar as Benign. ClinVar VariationId is 291608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3 link	c.*1159G>A	3_prime_UTR_variant	Exon 49 of 49	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1 link	c.*1159G>A	3_prime_UTR_variant	Exon 49 of 49		NP_001352881.1
KIF1B	NM_015074.3 link	c.*1159G>A	3_prime_UTR_variant	Exon 47 of 47		NP_055889.2	O60333-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1 link	c.*1159G>A		3_prime_UTR_variant	Exon 49 of 49		NM_001365951.3	ENSP00000502065.1		O60333-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15349

AN:

152062

Hom.:

949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0911

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.00695

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.109

AC:

3641

AN:

33374

Hom.:

234

Cov.:

AF XY:

0.111

AC XY:

1722

AN XY:

15520

show subpopulations

African (AFR)

AF:

0.0437

AC:

AN:

1212

American (AMR)

AF:

0.0901

AC:

AN:

788

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

410

AN:

2092

East Asian (EAS)

AF:

0.0159

AC:

AN:

6164

South Asian (SAS)

AF:

0.199

AC:

AN:

458

European-Finnish (FIN)

AF:

0.192

AC:

AN:

Middle Eastern (MID)

AF:

0.126

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.129

AC:

2547

AN:

19724

Other (OTH)

AF:

0.126

AC:

340

AN:

2704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

153

306

458

611

764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.101

AC:

15346

AN:

152180

Hom.:

948

Cov.:

AF XY:

0.101

AC XY:

7504

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0545

AC:

2265

AN:

41538

American (AMR)

AF:

0.0909

AC:

1390

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

691

AN:

3468

East Asian (EAS)

AF:

0.00697

AC:

AN:

5168

South Asian (SAS)

AF:

0.182

AC:

879

AN:

4824

European-Finnish (FIN)

AF:

0.107

AC:

1132

AN:

10588

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8579

AN:

67994

Other (OTH)

AF:

0.113

AC:

238

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

693

1386

2078

2771

3464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.105

Hom.:

129

Bravo

AF:

0.0960

Asia WGS

AF:

0.0880

AC:

306

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuroblastoma

Benign:1

Jan 13, 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

(source)

DANN

Benign

0.70

PhyloP100

0.95

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