rs2004034

Variant names:

• chr1-10307366-G-A
• rs2004034
• ENST00000377093.9:c.*2719G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377093.9(KIF1B):​c.*2719G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 836,042 control chromosomes in the GnomAD database, including 35,660 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 (5015 hom., cov: 32)
  • Exomes 𝑓: 0.30 (30645 hom.)
• Consequence: KIF1B ENST00000377093.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377093.9. 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.2115+10120G>A		intron	N/A	NP_001352880.1
	KIF1B	NM_001365953.1		c.*2719G>A		3_prime_UTR	Exon 21 of 21	NP_001352882.1
	KIF1B	NM_183416.4		c.*2719G>A		3_prime_UTR	Exon 21 of 21	NP_904325.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	ENST00000377093.9	TSL:1	c.*2719G>A		3_prime_UTR	Exon 21 of 21	ENSP00000366297.4
	KIF1B	ENST00000676179.1	MANE Select	c.2115+10120G>A		intron	N/A	ENSP00000502065.1
	KIF1B	ENST00000377081.5	TSL:1	c.2115+10120G>A		intron	N/A	ENSP00000366284.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36182 AN: 152062 Hom.: 5002 Cov.: 32

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.297 AC: 203449 AN: 683862 Hom.: 30645 Cov.: 9 AF XY: 0.298 AC XY: 95104 AN XY: 318876

African (AFR) AF: 0.0708 AC: 921 AN: 13000

American (AMR) AF: 0.285 AC: 348 AN: 1222

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 1472 AN: 5460

East Asian (EAS) AF: 0.259 AC: 1968 AN: 7588

South Asian (SAS) AF: 0.235 AC: 3129 AN: 13306

European-Finnish (FIN) AF: 0.271 AC: 65 AN: 240

Middle Eastern (MID) AF: 0.211 AC: 306 AN: 1450

European-Non Finnish (NFE) AF: 0.305 AC: 188372 AN: 618166

Other (OTH) AF: 0.293 AC: 6868 AN: 23430

GnomAD4 genome AF: 0.238 AC: 36213 AN: 152180 Hom.: 5015 Cov.: 32 AF XY: 0.239 AC XY: 17787 AN XY: 74400

African (AFR) AF: 0.0919 AC: 3818 AN: 41538

American (AMR) AF: 0.313 AC: 4778 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5186

South Asian (SAS) AF: 0.246 AC: 1187 AN: 4824

European-Finnish (FIN) AF: 0.292 AC: 3088 AN: 10576

Middle Eastern (MID) AF: 0.203 AC: 59 AN: 290

European-Non Finnish (NFE) AF: 0.294 AC: 20004 AN: 67994

Other (OTH) AF: 0.260 AC: 550 AN: 2112

Alfa AF: 0.261 Hom.: 727

Bravo AF: 0.235

Asia WGS AF: 0.272 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.48
PhyloP100		0.68
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: rs2004034; hg19: chr1-10367424;