rs2004034

Positions:

• chr1-10307366-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.2115+10120G>A		intron_variant		ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.2115+10120G>A		intron_variant			NM_001365951.3	ENSP00000502065	P1

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

Gnomad4 AFR exome AF: 0.0708

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.293

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

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.260

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2004034; hg19: chr1-10367424;