rs17034660

Variant names:

• chr1-10282464-G-A
• rs17034660
• NM_001365951.3:c.1365G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-10282464-G-A
• chr1-10282464-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001365951.3(KIF1B):​c.1365G>A​(p.Thr455Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,006 control chromosomes in the GnomAD database, including 760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T455T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.035 (113 hom., cov: 32)
  • Exomes 𝑓: 0.026 (647 hom.)
• Consequence: KIF1B NM_001365951.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.468
• Publications: 8 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-10282464-G-A is Benign according to our data. Variant chr1-10282464-G-A is described in ClinVar as Benign. ClinVar VariationId is 291522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.468 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0677 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	NM_001365951.3	MANE Select	c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	NP_001352880.1
	KIF1B	NM_001365952.1		c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	NP_001352881.1
	KIF1B	NM_015074.3		c.1227G>A	p.Thr409Thr	synonymous	Exon 13 of 47	NP_055889.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	ENST00000676179.1	MANE Select	c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	ENSP00000502065.1
	KIF1B	ENST00000377081.5	TSL:1	c.1365G>A	p.Thr455Thr	synonymous	Exon 14 of 48	ENSP00000366284.1
	KIF1B	ENST00000377086.5	TSL:1	c.1365G>A	p.Thr455Thr	synonymous	Exon 15 of 49	ENSP00000366290.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5344 AN: 152098 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0406

GnomAD2 exomes AF: 0.0330 AC: 8292 AN: 251286 AF XY: 0.0320

Gnomad AFR exome AF: 0.0497

Gnomad AMR exome AF: 0.0295

Gnomad ASJ exome AF: 0.0464

Gnomad EAS exome AF: 0.0750

Gnomad FIN exome AF: 0.0464

Gnomad NFE exome AF: 0.0233

Gnomad OTH exome AF: 0.0372

GnomAD4 exome AF: 0.0256 AC: 37434 AN: 1461790 Hom.: 647 Cov.: 34 AF XY: 0.0255 AC XY: 18539 AN XY: 727206

African (AFR) AF: 0.0507 AC: 1697 AN: 33480

American (AMR) AF: 0.0305 AC: 1366 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 1213 AN: 26136

East Asian (EAS) AF: 0.0836 AC: 3317 AN: 39698

South Asian (SAS) AF: 0.0257 AC: 2216 AN: 86256

European-Finnish (FIN) AF: 0.0464 AC: 2480 AN: 53418

Middle Eastern (MID) AF: 0.0830 AC: 479 AN: 5768

European-Non Finnish (NFE) AF: 0.0204 AC: 22640 AN: 1111918

Other (OTH) AF: 0.0335 AC: 2026 AN: 60392

GnomAD4 genome AF: 0.0351 AC: 5349 AN: 152216 Hom.: 113 Cov.: 32 AF XY: 0.0361 AC XY: 2683 AN XY: 74416

African (AFR) AF: 0.0481 AC: 1998 AN: 41516

American (AMR) AF: 0.0313 AC: 479 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3472

East Asian (EAS) AF: 0.0738 AC: 382 AN: 5174

South Asian (SAS) AF: 0.0268 AC: 129 AN: 4820

European-Finnish (FIN) AF: 0.0502 AC: 532 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1489 AN: 68020

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0278 Hom.: 108

Bravo AF: 0.0353

Asia WGS AF: 0.0610 AC: 212 AN: 3478

EpiCase AF: 0.0264

EpiControl AF: 0.0228

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Jul 28, 2020

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Charcot-Marie-Tooth disease Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Neuroblastoma Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Charcot-Marie-Tooth disease type 2 Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hereditary cancer-predisposing syndrome Benign:1

Jul 08, 2025

Molecular Diagnostics Laboratory, Catalan Institute of Oncology

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BA1, BP4, BP7 c.1227G>A located in exon 13 of the KIF1B gene is predicted to result in no splicing alteration (according to SpliceAI) and no amino acid change, p.(Thr409=)(BP4, BP7). The variant allele was found in 8999/268140 alleles (177 homozygous), with a filtering allele frequency of 3.27% at 99% confidence, in the gnomAD v2.1.1 database (non-cancer data set)(BA1). To our knowledge, neither relevant clinical data nor functional studies have been reported for this variant. This variant has been identified in the ClinVar database (6x benign) but has not been identified in the LOVD database. Based on currently available information, c.1227G>A is classified as a benign variant according ACMG guidelines.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.5
DANN	Benign	0.70
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs17034660; hg19: chr1-10342522; COSMIC: COSV55805260; COSMIC: COSV55805260;