1-10232301-C-CAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001365951.3(KIF1B):c.-16_-15dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,429,268 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (8 hom.)
• Consequence: KIF1B NM_001365951.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.439

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 -10 ACMG points.

• BP6: Variant 1-10232301-C-CAT is Benign according to our data. Variant chr1-10232301-C-CAT is described in ClinVar as [Likely_benign]. Clinvar id is 291463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00619 (937/151448) while in subpopulation AFR AF= 0.0175 (722/41336). AF 95% confidence interval is 0.0164. There are 7 homozygotes in gnomad4. There are 447 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 931 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.-16_-15dup		5_prime_UTR_variant	2/49	ENST00000676179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1B	ENST00000676179.1	c.-16_-15dup		5_prime_UTR_variant	2/49		NM_001365951.3	P1

Frequencies

GnomAD3 genomes AF: 0.00615 AC: 931 AN: 151332 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00390

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000944

Gnomad OTH AF: 0.00724

GnomAD3 exomes AF: 0.00361 AC: 695 AN: 192740 Hom.: 2 AF XY: 0.00301 AC XY: 310 AN XY: 103150

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.00236

Gnomad ASJ exome AF: 0.000480

Gnomad EAS exome AF: 0.0136

Gnomad SAS exome AF: 0.00233

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.00395

GnomAD4 exome AF: 0.00197 AC: 2514 AN: 1277820 Hom.: 8 Cov.: 18 AF XY: 0.00189 AC XY: 1217 AN XY: 642358

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.00213

Gnomad4 ASJ exome AF: 0.000530

Gnomad4 EAS exome AF: 0.00866

Gnomad4 SAS exome AF: 0.00203

Gnomad4 FIN exome AF: 0.000135

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.00619 AC: 937 AN: 151448 Hom.: 7 Cov.: 31 AF XY: 0.00604 AC XY: 447 AN XY: 73990

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00389

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000944

Gnomad4 OTH AF: 0.00764

Bravo AF: 0.00678

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Neuroblastoma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pheochromocytoma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Charcot-Marie-Tooth disease type 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34063243; hg19: chr1-10292359;