1-10331478-T-G

Variant names:

• chr1-10331478-T-G
• rs12734551
• NM_001365951.3:c.2925-3042T>G

Variant summary

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

The NM_001365951.3(KIF1B):​c.2925-3042T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,194 control chromosomes in the GnomAD database, including 5,232 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 0.25 (5232 hom., cov: 32)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 10 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: ClinGen, Orphanet, Ambry Genetics, 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	NM_001365951.3	MANE Select	c.2925-3042T>G		intron	N/A	NP_001352880.1	O60333-1
	KIF1B	NM_001365952.1		c.2925-3042T>G		intron	N/A	NP_001352881.1	O60333-1
	KIF1B	NM_015074.3		c.2787-3042T>G		intron	N/A	NP_055889.2	O60333-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	ENST00000676179.1	MANE Select	c.2925-3042T>G		intron	N/A	ENSP00000502065.1	O60333-1
	KIF1B	ENST00000377081.5	TSL:1	c.2925-3042T>G		intron	N/A	ENSP00000366284.1	O60333-4
	KIF1B	ENST00000377086.5	TSL:1	c.2925-3042T>G		intron	N/A	ENSP00000366290.1	O60333-1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37451 AN: 152076 Hom.: 5217 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.246 AC: 37501 AN: 152194 Hom.: 5232 Cov.: 32 AF XY: 0.247 AC XY: 18413 AN XY: 74396

African (AFR) AF: 0.113 AC: 4704 AN: 41542

American (AMR) AF: 0.315 AC: 4817 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1467 AN: 5184

South Asian (SAS) AF: 0.250 AC: 1207 AN: 4824

European-Finnish (FIN) AF: 0.294 AC: 3117 AN: 10588

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20251 AN: 67974

Other (OTH) AF: 0.263 AC: 555 AN: 2110

Alfa AF: 0.200 Hom.: 665

Bravo AF: 0.244

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.66
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12734551; hg19: chr1-10391536;