rs6541085

chr1-10225651-A-Gchr1-10225651-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.-79-6599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,964 control chromosomes in the GnomAD database, including 21,758 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 0.53 (21758 hom., cov: 32)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.-79-6599A>G		intron_variant		ENST00000676179.1
KIF1B	NM_001365952.1	c.-79-6599A>G		intron_variant
KIF1B	NM_015074.3	c.-79-6599A>G		intron_variant
KIF1B	NM_183416.4	c.-79-6599A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1B	ENST00000676179.1	c.-79-6599A>G		intron_variant			NM_001365951.3	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80046 AN: 151846 Hom.: 21714 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.527 AC: 80148 AN: 151964 Hom.: 21758 Cov.: 32 AF XY: 0.525 AC XY: 39011 AN XY: 74266

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.529

Alfa AF: 0.481 Hom.: 21742

Bravo AF: 0.535

Asia WGS AF: 0.455 AC: 1581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.65
Dann	Benign	0.51

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: rs6541085; hg19: chr1-10285709;