chr1-10285714-T-C

Variant names:

• chr1-10285714-T-C
• rs12120191
• NM_001365951.3:c.1434+3181T>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.1434+3181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,982 control chromosomes in the GnomAD database, including 8,770 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 0.34 (8770 hom., cov: 31)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 8 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.368 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.1434+3181T>C		intron	N/A	NP_001352880.1
	KIF1B	NM_001365952.1		c.1434+3181T>C		intron	N/A	NP_001352881.1
	KIF1B	NM_015074.3		c.1296+3181T>C		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.1434+3181T>C		intron	N/A	ENSP00000502065.1
	KIF1B	ENST00000377081.5	TSL:1	c.1434+3181T>C		intron	N/A	ENSP00000366284.1
	KIF1B	ENST00000377086.5	TSL:1	c.1434+3181T>C		intron	N/A	ENSP00000366290.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51089 AN: 151864 Hom.: 8744 Cov.: 31

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.337 AC: 51163 AN: 151982 Hom.: 8770 Cov.: 31 AF XY: 0.338 AC XY: 25105 AN XY: 74276

African (AFR) AF: 0.300 AC: 12440 AN: 41438

American (AMR) AF: 0.377 AC: 5750 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1149 AN: 3466

East Asian (EAS) AF: 0.357 AC: 1848 AN: 5170

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4820

European-Finnish (FIN) AF: 0.386 AC: 4082 AN: 10564

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23392 AN: 67940

Other (OTH) AF: 0.340 AC: 717 AN: 2110

Alfa AF: 0.346 Hom.: 14414

Bravo AF: 0.337

Asia WGS AF: 0.347 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		0.17
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: rs12120191; hg19: chr1-10345772;