rs17396340

Variant names:

• chr1-10226118-G-A
• rs17396340
• NM_001365951.3:c.-79-6132G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-10226118-G-A
• chr1-10226118-G-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.-79-6132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,204 control chromosomes in the GnomAD database, including 1,038 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 0.11 (1038 hom., cov: 32)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.-79-6132G>A		intron_variant	Intron 1 of 48	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1	c.-79-6132G>A		intron_variant	Intron 1 of 48		NP_001352881.1
KIF1B	NM_015074.3	c.-79-6132G>A		intron_variant	Intron 1 of 46		NP_055889.2
KIF1B	NM_183416.4	c.-79-6132G>A		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.-79-6132G>A		intron_variant	Intron 1 of 48		NM_001365951.3	ENSP00000502065.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16347 AN: 152086 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00730

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.107 AC: 16344 AN: 152204 Hom.: 1038 Cov.: 32 AF XY: 0.107 AC XY: 7940 AN XY: 74426

African (AFR) AF: 0.0691 AC: 2872 AN: 41534

American (AMR) AF: 0.0929 AC: 1419 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.00732 AC: 38 AN: 5192

South Asian (SAS) AF: 0.176 AC: 848 AN: 4812

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10600

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8891 AN: 67994

Other (OTH) AF: 0.115 AC: 244 AN: 2116

Alfa AF: 0.114 Hom.: 2070

Bravo AF: 0.103

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.056
Mutation Taster		=99/1	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: rs17396340; hg19: chr1-10286176;