chr1-10278540-A-G

Variant names:

• chr1-10278540-A-G
• rs10492970
• NM_001365951.3:c.1180+412A>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.1180+412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 236,118 control chromosomes in the GnomAD database, including 158 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 0.034 (106 hom., cov: 32)
  • Exomes 𝑓: 0.029 (52 hom.)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 3 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: ClinGen, Orphanet, Ambry Genetics, 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0682 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	NM_001365951.3	MANE Select	c.1180+412A>G		intron	N/A	NP_001352880.1	O60333-1
	KIF1B	NM_001365952.1		c.1180+412A>G		intron	N/A	NP_001352881.1	O60333-1
	KIF1B	NM_015074.3		c.1162+412A>G		intron	N/A	NP_055889.2	O60333-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	ENST00000676179.1	MANE Select	c.1180+412A>G		intron	N/A	ENSP00000502065.1	O60333-1
	KIF1B	ENST00000377081.5	TSL:1	c.1180+412A>G		intron	N/A	ENSP00000366284.1	O60333-4
	KIF1B	ENST00000377086.5	TSL:1	c.1180+412A>G		intron	N/A	ENSP00000366290.1	O60333-1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5143 AN: 152154 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0289 AC: 2424 AN: 83846 Hom.: 52 Cov.: 0 AF XY: 0.0281 AC XY: 1268 AN XY: 45196

African (AFR) AF: 0.0339 AC: 39 AN: 1152

American (AMR) AF: 0.0409 AC: 156 AN: 3816

Ashkenazi Jewish (ASJ) AF: 0.0411 AC: 78 AN: 1900

East Asian (EAS) AF: 0.0823 AC: 267 AN: 3246

South Asian (SAS) AF: 0.0246 AC: 345 AN: 13998

European-Finnish (FIN) AF: 0.0419 AC: 157 AN: 3744

Middle Eastern (MID) AF: 0.0541 AC: 17 AN: 314

European-Non Finnish (NFE) AF: 0.0237 AC: 1221 AN: 51462

Other (OTH) AF: 0.0342 AC: 144 AN: 4214

GnomAD4 genome AF: 0.0338 AC: 5149 AN: 152272 Hom.: 106 Cov.: 32 AF XY: 0.0348 AC XY: 2589 AN XY: 74442

African (AFR) AF: 0.0450 AC: 1868 AN: 41542

American (AMR) AF: 0.0297 AC: 455 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3468

East Asian (EAS) AF: 0.0743 AC: 385 AN: 5184

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4822

European-Finnish (FIN) AF: 0.0505 AC: 536 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1447 AN: 68028

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0266 Hom.: 75

Bravo AF: 0.0338

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism

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: rs10492970; hg19: chr1-10338598;