1-10210657-GCC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001365951.3(KIF1B):c.-299_-298del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,248 control chromosomes in the GnomAD database, including 4,855 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4839 hom., cov: 25)
  • Exomes 𝑓: 0.19 (16 hom.)
• Consequence: KIF1B NM_001365951.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.241

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 1-10210657-GCC-G is Benign according to our data. Variant chr1-10210657-GCC-G is described in ClinVar as [Benign]. Clinvar id is 1224051.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.-299_-298del		5_prime_UTR_variant	1/49	ENST00000676179.1
KIF1B	NM_183416.4	c.-299_-298del		5_prime_UTR_variant	1/21
KIF1B	NM_015074.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1B	ENST00000676179.1	c.-299_-298del		5_prime_UTR_variant	1/49		NM_001365951.3	P1
KIF1B	ENST00000377093.9	c.-299_-298del		5_prime_UTR_variant	1/21	1
KIF1B	ENST00000696500.1	c.-299_-298del		5_prime_UTR_variant, NMD_transcript_variant	1/22

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37292 AN: 151298 Hom.: 4820 Cov.: 25

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.189 AC: 159 AN: 842 Hom.: 16 AF XY: 0.195 AC XY: 124 AN XY: 636

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.0556

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.247 AC: 37348 AN: 151406 Hom.: 4839 Cov.: 25 AF XY: 0.247 AC XY: 18293 AN XY: 74006

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.260

Alfa AF: 0.257 Hom.: 649

Bravo AF: 0.247

Asia WGS AF: 0.279 AC: 946 AN: 3400

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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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: rs140167753; hg19: chr1-10270715;