Variant rs3748578 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365951.3(KIF1B):c.4056-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 992,654 control chromosomes in the GnomAD database, including 44,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6599 hom., cov: 31)

Exomes 𝑓: 0.30 ( 37709 hom. )

Consequence

KIF1B
NM_001365951.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.694

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-10360860-G-A is Benign according to our data. Variant chr1-10360860-G-A is described in ClinVar as [Benign]. Clinvar id is 1292713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
KIF1B	NM_001365951.3 link	c.4056-69G>A	intron_variant	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1 link	c.4056-69G>A	intron_variant		NP_001352881.1
KIF1B	NM_015074.3 link	c.3918-69G>A	intron_variant		NP_055889.2	O60333-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1 link	c.4056-69G>A		intron_variant			NM_001365951.3	ENSP00000502065.1		O60333-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44370

AN:

151914

Hom.:

6576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.290

GnomAD4 exome

AF:

0.298

AC:

250510

AN:

840622

Hom.:

37709

AF XY:

0.295

AC XY:

130807

AN XY:

443696

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.295

GnomAD4 genome

AF:

0.292

AC:

44443

AN:

152032

Hom.:

6599

Cov.:

AF XY:

0.293

AC XY:

21734

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.301

Hom.:

10600

Bravo

AF:

0.296

Asia WGS

AF:

0.286

AC:

992

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.47

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over