Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001365951.3(KIF1B):c.1365G>A(p.Thr455Thr) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T455T) has been classified as Likely 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:7

Conservation

PhyloP100: 0.468

Publications

8 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 -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 VariationId is 291522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

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	HGVSp	Effect	Exon Rank	Protein
KIF1B	NM_001365951.3	MANE Select	c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	NP_001352880.1
KIF1B	NM_001365952.1		c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	NP_001352881.1
KIF1B	NM_015074.3		c.1227G>A	p.Thr409Thr	synonymous	Exon 13 of 47	NP_055889.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KIF1B	ENST00000676179.1	MANE Select	c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	ENSP00000502065.1
KIF1B	ENST00000377081.5	TSL:1	c.1365G>A	p.Thr455Thr	synonymous	Exon 14 of 48	ENSP00000366284.1
KIF1B	ENST00000377086.5	TSL:1	c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	ENSP00000366290.1

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

GnomAD2 exomes

AF:

0.0330

AC:

8292

AN:

251286

AF XY:

0.0320

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 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

African (AFR)

AF:

0.0507

AC:

1697

AN:

33480

American (AMR)

AF:

0.0305

AC:

1366

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

1213

AN:

26136

East Asian (EAS)

AF:

0.0836

AC:

3317

AN:

39698

South Asian (SAS)

AF:

0.0257

AC:

2216

AN:

86256

European-Finnish (FIN)

AF:

0.0464

AC:

2480

AN:

53418

Middle Eastern (MID)

AF:

0.0830

AC:

479

AN:

5768

European-Non Finnish (NFE)

AF:

0.0204

AC:

22640

AN:

1111918

Other (OTH)

AF:

0.0335

AC:

2026

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

2224

4448

6672

8896

11120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.0351

AC:

5349

AN:

152216

Hom.:

113

Cov.:

AF XY:

0.0361

AC XY:

2683

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0481

AC:

1998

AN:

41516

American (AMR)

AF:

0.0313

AC:

479

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0516

AC:

179

AN:

3472

East Asian (EAS)

AF:

0.0738

AC:

382

AN:

5174

South Asian (SAS)

AF:

0.0268

AC:

129

AN:

4820

European-Finnish (FIN)

AF:

0.0502

AC:

532

AN:

10602

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0219

AC:

1489

AN:

68020

Other (OTH)

AF:

0.0402

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

253

507

760

1014

1267

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:

0.0278

Hom.:

108

Bravo

AF:

0.0353

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

EpiCase

AF:

0.0264

EpiControl

AF:

0.0228

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Charcot-Marie-Tooth disease (1)

Charcot-Marie-Tooth disease type 2 (1)

Hereditary cancer-predisposing syndrome (1)

Neuroblastoma (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.5

(source)

DANN

Benign

0.70

PhyloP100

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over