NM_001365951.3:c.2675+518A>G

Variant names:

• chr1-10325413-A-G
• rs17401966
• NM_001365951.3:c.2675+518A>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.2675+518A>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 152,040 control chromosomes in the GnomAD database, including 5,118 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 (5118 hom., cov: 31)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 90 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.2675+518A>G		intron_variant	Intron 26 of 48	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1	c.2675+518A>G		intron_variant	Intron 26 of 48		NP_001352881.1
KIF1B	NM_015074.3	c.2537+518A>G		intron_variant	Intron 24 of 46		NP_055889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.2675+518A>G		intron_variant	Intron 26 of 48		NM_001365951.3	ENSP00000502065.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36539 AN: 151922 Hom.: 5106 Cov.: 31

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.241 AC: 36570 AN: 152040 Hom.: 5118 Cov.: 31 AF XY: 0.242 AC XY: 17951 AN XY: 74316

African (AFR) AF: 0.0929 AC: 3852 AN: 41482

American (AMR) AF: 0.313 AC: 4783 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1470 AN: 5176

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4812

European-Finnish (FIN) AF: 0.294 AC: 3107 AN: 10562

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

European-Non Finnish (NFE) AF: 0.298 AC: 20225 AN: 67950

Other (OTH) AF: 0.260 AC: 547 AN: 2106

Alfa AF: 0.281 Hom.: 21527

Bravo AF: 0.238

Asia WGS AF: 0.273 AC: 948 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.86
PhyloP100		0.12
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: rs17401966; hg19: chr1-10385471;