rs3753037

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1777+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,603,204 control chromosomes in the GnomAD database, including 68,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5595 hom., cov: 31)

Exomes 𝑓: 0.29 ( 62856 hom. )

Consequence

KIF1B
NM_001365951.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.262

Publications

15 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: ClinGen, Orphanet, Ambry Genetics, 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=-0.81).

BP6

Variant 1-10295776-C-T is Benign according to our data. Variant chr1-10295776-C-T is described in ClinVar as Benign. ClinVar VariationId is 177960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF1B	NM_001365951.3	MANE Select	c.1777+10C>T	intron	N/A	NP_001352880.1	O60333-1
KIF1B	NM_001365952.1		c.1777+10C>T	intron	N/A	NP_001352881.1	O60333-1
KIF1B	NM_015074.3		c.1639+10C>T	intron	N/A	NP_055889.2	O60333-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF1B	ENST00000676179.1	MANE Select	c.1777+10C>T	intron	N/A	ENSP00000502065.1	O60333-1
KIF1B	ENST00000377081.5	TSL:1	c.1777+10C>T	intron	N/A	ENSP00000366284.1	O60333-4
KIF1B	ENST00000377086.5	TSL:1	c.1777+10C>T	intron	N/A	ENSP00000366290.1	O60333-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40398

AN:

151908

Hom.:

5574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.272

GnomAD2 exomes

AF:

0.284

AC:

71355

AN:

250910

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.350

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.293

AC:

424561

AN:

1451178

Hom.:

62856

Cov.:

AF XY:

0.291

AC XY:

210002

AN XY:

722420

show subpopulations

African (AFR)

AF:

0.182

AC:

6065

AN:

33276

American (AMR)

AF:

0.343

AC:

15315

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

7195

AN:

26056

East Asian (EAS)

AF:

0.257

AC:

10166

AN:

39626

South Asian (SAS)

AF:

0.226

AC:

19424

AN:

85988

European-Finnish (FIN)

AF:

0.301

AC:

16021

AN:

53236

Middle Eastern (MID)

AF:

0.207

AC:

1142

AN:

5512

European-Non Finnish (NFE)

AF:

0.301

AC:

331873

AN:

1102774

Other (OTH)

AF:

0.289

AC:

17360

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

14533

29066

43600

58133

72666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10868

21736

32604

43472

54340

<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:

0.266

AC:

40461

AN:

152026

Hom.:

5595

Cov.:

AF XY:

0.267

AC XY:

19805

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.190

AC:

7877

AN:

41472

American (AMR)

AF:

0.324

AC:

4948

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

939

AN:

3466

East Asian (EAS)

AF:

0.284

AC:

1467

AN:

5162

South Asian (SAS)

AF:

0.239

AC:

1152

AN:

4822

European-Finnish (FIN)

AF:

0.292

AC:

3079

AN:

10560

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.294

AC:

20012

AN:

67970

Other (OTH)

AF:

0.277

AC:

584

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1483

2967

4450

5934

7417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.280

Hom.:

2264

Bravo

AF:

0.267

Asia WGS

AF:

0.278

AC:

963

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Charcot-Marie-Tooth disease (1)

Charcot-Marie-Tooth disease type 2 (1)

Charcot-Marie-Tooth disease type 2A1 (1)

Neuroblastoma (1)

Pheochromocytoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.3

(source)

DANN

Benign

0.47

PhyloP100

0.26

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over