rs12131785

Positions:

• chr1-10281458-C-T

Variant summary

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

The NM_001365951.3(KIF1B):​c.1223-864C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,992 control chromosomes in the GnomAD database, including 2,062 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 0.14 (2062 hom., cov: 32)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.1223-864C>T		intron_variant		ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.1223-864C>T		intron_variant			NM_001365951.3	ENSP00000502065	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21917 AN: 151874 Hom.: 2062 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.144 AC: 21908 AN: 151992 Hom.: 2062 Cov.: 32 AF XY: 0.140 AC XY: 10419 AN XY: 74280

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.163

Alfa AF: 0.189 Hom.: 1500

Bravo AF: 0.140

Asia WGS AF: 0.0300 AC: 104 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.1
DANN	Benign	0.56

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: rs12131785; hg19: chr1-10341516;