dbSNP rs41274464: KIF1B:c.*2353G>A (chr1-10307000-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000377093.9(KIF1B):c.*2353G>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 0.0248 in 1,041,774 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 42 hom., cov: 31)

Exomes 𝑓: 0.026 ( 350 hom. )

Consequence

KIF1B
ENST00000377093.9 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.276

Publications

2 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 links:

RN7SL731P (HGNC:46747): (RNA, 7SL, cytoplasmic 731, pseudogene)

RN7SL731P links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0188 (2855/152178) while in subpopulation NFE AF = 0.0279 (1898/68006). AF 95% confidence interval is 0.0269. There are 42 homozygotes in GnomAd4. There are 1426 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 2855 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3 link	c.2115+9754G>A		intron_variant	Intron 22 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.2115+9754G>A		intron_variant	Intron 22 of 48		NM_001365951.3	ENSP00000502065.1		O60333-1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2855

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0142

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0444

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.0259

AC:

23030

AN:

889596

Hom.:

350

Cov.:

AF XY:

0.0259

AC XY:

10635

AN XY:

410880

show subpopulations

African (AFR)

AF:

0.00295

AC:

AN:

18326

American (AMR)

AF:

0.0107

AC:

AN:

2626

Ashkenazi Jewish (ASJ)

AF:

0.00567

AC:

AN:

8818

East Asian (EAS)

AF:

0.0000809

AC:

AN:

12354

South Asian (SAS)

AF:

0.00236

AC:

AN:

16960

European-Finnish (FIN)

AF:

0.0411

AC:

AN:

316

Middle Eastern (MID)

AF:

0.00152

AC:

AN:

1970

European-Non Finnish (NFE)

AF:

0.0279

AC:

22212

AN:

796236

Other (OTH)

AF:

0.0197

AC:

629

AN:

31990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1039

2078

3117

4156

5195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1084

2168

3252

4336

5420

<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:

0.0188

AC:

2855

AN:

152178

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1426

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00465

AC:

193

AN:

41520

American (AMR)

AF:

0.0141

AC:

216

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0444

AC:

470

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0279

AC:

1898

AN:

68006

Other (OTH)

AF:

0.0114

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

153

306

460

613

766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0221

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.6

(source)

DANN

Benign

0.76

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over