rs41274464

Positions:

• chr1-10307000-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_183416.4(KIF1B):​c.*2353G>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 0.0248 in 1,041,774 control chromosomes in the GnomAD database, including 392 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 0.019 (42 hom., cov: 31)
  • Exomes 𝑓: 0.026 (350 hom.)
• Consequence: KIF1B NM_183416.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

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=-0.58).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2855/152178) while in subpopulation NFE AF= 0.0279 (1898/68006). AF 95% confidence interval is 0.0269. There are 42 homozygotes in gnomad4. There are 1426 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2855 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.2115+9754G>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+9754G>A		intron_variant			NM_001365951.3	ENSP00000502065.1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2855 AN: 152060 Hom.: 42 Cov.: 31

Gnomad AFR AF: 0.00466

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0259 AC: 23030 AN: 889596 Hom.: 350 Cov.: 32 AF XY: 0.0259 AC XY: 10635 AN XY: 410880

Gnomad4 AFR exome AF: 0.00295

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00567

Gnomad4 EAS exome AF: 0.0000809

Gnomad4 SAS exome AF: 0.00236

Gnomad4 FIN exome AF: 0.0411

Gnomad4 NFE exome AF: 0.0279

Gnomad4 OTH exome AF: 0.0197

GnomAD4 genome AF: 0.0188 AC: 2855 AN: 152178 Hom.: 42 Cov.: 31 AF XY: 0.0192 AC XY: 1426 AN XY: 74390

Gnomad4 AFR AF: 0.00465

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0209 Hom.: 6

Bravo AF: 0.0156

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.6
DANN	Benign	0.76

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: rs41274464; hg19: chr1-10367058;