1-10225651-A-G

Variant names:

• chr1-10225651-A-G
• rs6541085
• NM_001365951.3:c.-79-6599A>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.-79-6599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,964 control chromosomes in the GnomAD database, including 21,758 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 0.53 (21758 hom., cov: 32)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 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.-79-6599A>G		intron	N/A	NP_001352880.1
	KIF1B	NM_001365952.1		c.-79-6599A>G		intron	N/A	NP_001352881.1
	KIF1B	NM_015074.3		c.-79-6599A>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.-79-6599A>G		intron	N/A	ENSP00000502065.1
	KIF1B	ENST00000377086.5	TSL:1	c.-79-6599A>G		intron	N/A	ENSP00000366290.1
	KIF1B	ENST00000263934.10	TSL:1	c.-79-6599A>G		intron	N/A	ENSP00000263934.6

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80046 AN: 151846 Hom.: 21714 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.527 AC: 80148 AN: 151964 Hom.: 21758 Cov.: 32 AF XY: 0.525 AC XY: 39011 AN XY: 74266

African (AFR) AF: 0.655 AC: 27174 AN: 41456

American (AMR) AF: 0.502 AC: 7647 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1880 AN: 5158

South Asian (SAS) AF: 0.445 AC: 2146 AN: 4822

European-Finnish (FIN) AF: 0.497 AC: 5241 AN: 10548

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32388 AN: 67962

Other (OTH) AF: 0.529 AC: 1116 AN: 2110

Alfa AF: 0.488 Hom.: 50575

Bravo AF: 0.535

Asia WGS AF: 0.455 AC: 1581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.51
PhyloP100		-0.94
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: rs6541085; hg19: chr1-10285709;