rs10492969

Variant names:

• chr1-10226300-T-C
• rs10492969
• NM_001365951.3:c.-79-5950T>C

Variant summary

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

The NM_001365951.3(KIF1B):​c.-79-5950T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,044 control chromosomes in the GnomAD database, including 23,903 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 (23903 hom., cov: 31)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.-79-5950T>C		intron_variant	Intron 1 of 48	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1	c.-79-5950T>C		intron_variant	Intron 1 of 48		NP_001352881.1
KIF1B	NM_015074.3	c.-79-5950T>C		intron_variant	Intron 1 of 46		NP_055889.2
KIF1B	NM_183416.4	c.-79-5950T>C		intron_variant	Intron 1 of 20		NP_904325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.-79-5950T>C		intron_variant	Intron 1 of 48		NM_001365951.3	ENSP00000502065.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83242 AN: 151926 Hom.: 23857 Cov.: 31

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.548 AC: 83350 AN: 152044 Hom.: 23903 Cov.: 31 AF XY: 0.546 AC XY: 40568 AN XY: 74324

African (AFR) AF: 0.725 AC: 30088 AN: 41492

American (AMR) AF: 0.511 AC: 7804 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3466

East Asian (EAS) AF: 0.366 AC: 1895 AN: 5182

South Asian (SAS) AF: 0.445 AC: 2149 AN: 4824

European-Finnish (FIN) AF: 0.499 AC: 5265 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32441 AN: 67930

Other (OTH) AF: 0.539 AC: 1141 AN: 2116

Alfa AF: 0.494 Hom.: 37093

Bravo AF: 0.558

Asia WGS AF: 0.459 AC: 1595 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	0.24
DANN	Benign	0.48
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: rs10492969; hg19: chr1-10286358;