rs912962

chr1-10288654-A-Cchr1-10288654-A-Gchr1-10288654-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365951.3(KIF1B):c.1435-2428A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,882 control chromosomes in the GnomAD database, including 23,526 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 0.55 (23526 hom., cov: 31)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.1435-2428A>C		intron_variant		ENST00000676179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1B	ENST00000676179.1	c.1435-2428A>C		intron_variant			NM_001365951.3	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82677 AN: 151764 Hom.: 23478 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.545 AC: 82787 AN: 151882 Hom.: 23526 Cov.: 31 AF XY: 0.543 AC XY: 40312 AN XY: 74232

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.538

Alfa AF: 0.500 Hom.: 5368

Bravo AF: 0.554

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.020
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs912962; hg19: chr1-10348712;