rs10492970

chr1-10278540-A-G

Variant summary

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

The NM_001365951.3(KIF1B):c.1180+412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 236,118 control chromosomes in the GnomAD database, including 158 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 0.034 (106 hom., cov: 32)
  • Exomes 𝑓: 0.029 (52 hom.)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.1180+412A>G		intron_variant		ENST00000676179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1B	ENST00000676179.1	c.1180+412A>G		intron_variant			NM_001365951.3	P1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5143 AN: 152154 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0289 AC: 2424 AN: 83846 Hom.: 52 Cov.: 0 AF XY: 0.0281 AC XY: 1268 AN XY: 45196

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.0409

Gnomad4 ASJ exome AF: 0.0411

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.0246

Gnomad4 FIN exome AF: 0.0419

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0342

GnomAD4 genome AF: 0.0338 AC: 5149 AN: 152272 Hom.: 106 Cov.: 32 AF XY: 0.0348 AC XY: 2589 AN XY: 74442

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.0263

Gnomad4 FIN AF: 0.0505

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0255 Hom.: 56

Bravo AF: 0.0338

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.8
Dann	Benign	0.52

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: rs10492970; hg19: chr1-10338598;