rs9332414

Variant names:

• chr1-10266905-C-T
• rs9332414
• NM_001365951.3:c.430-475C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365951.3(KIF1B):​c.430-475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,928 control chromosomes in the GnomAD database, including 8,580 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 0.33 (8580 hom., cov: 32)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• pheochromocytoma

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 2A1

  Inheritance: AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neuroblastoma, susceptibility to, 1

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.430-475C>T		intron_variant	Intron 5 of 48	ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.430-475C>T		intron_variant	Intron 5 of 48		NM_001365951.3	ENSP00000502065.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50302 AN: 151810 Hom.: 8558 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.332 AC: 50367 AN: 151928 Hom.: 8580 Cov.: 32 AF XY: 0.333 AC XY: 24742 AN XY: 74244

African (AFR) AF: 0.281 AC: 11627 AN: 41422

American (AMR) AF: 0.374 AC: 5703 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1135 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1859 AN: 5162

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4812

European-Finnish (FIN) AF: 0.394 AC: 4153 AN: 10530

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23400 AN: 67962

Other (OTH) AF: 0.337 AC: 712 AN: 2110

Alfa AF: 0.336 Hom.: 1852

Bravo AF: 0.330

Asia WGS AF: 0.346 AC: 1202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.057
DANN	Benign	0.64
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9332414; hg19: chr1-10326963;