rs11576866

Variant names:

• chr1-10354374-A-G
• rs11576866
• NM_001365951.3:c.4055+1638A>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.4055+1638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,122 control chromosomes in the GnomAD database, including 5,123 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 0.24 (5123 hom., cov: 32)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.306 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.4055+1638A>G		intron	N/A	NP_001352880.1
	KIF1B	NM_001365952.1		c.4055+1638A>G		intron	N/A	NP_001352881.1
	KIF1B	NM_015074.3		c.3917+1638A>G		intron	N/A	NP_055889.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	ENST00000676179.1	MANE Select	c.4055+1638A>G		intron	N/A	ENSP00000502065.1
	KIF1B	ENST00000377081.5	TSL:1	c.4055+1638A>G		intron	N/A	ENSP00000366284.1
	KIF1B	ENST00000377086.5	TSL:1	c.4055+1638A>G		intron	N/A	ENSP00000366290.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36569 AN: 152004 Hom.: 5111 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.241 AC: 36600 AN: 152122 Hom.: 5123 Cov.: 32 AF XY: 0.242 AC XY: 17981 AN XY: 74364

African (AFR) AF: 0.0931 AC: 3865 AN: 41516

American (AMR) AF: 0.313 AC: 4781 AN: 15278

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

East Asian (EAS) AF: 0.284 AC: 1471 AN: 5186

South Asian (SAS) AF: 0.250 AC: 1203 AN: 4814

European-Finnish (FIN) AF: 0.295 AC: 3112 AN: 10550

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20241 AN: 67996

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.263 Hom.: 737

Bravo AF: 0.238

Asia WGS AF: 0.273 AC: 946 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.40
PhyloP100		-0.85
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: rs11576866; hg19: chr1-10414432;