1-10210698-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001365951.3(KIF1B):c.-260C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 151,528 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: KIF1B NM_001365951.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -1.25

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-10210698-C-T is Benign according to our data. Variant chr1-10210698-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 368793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 269 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.-260C>T		5_prime_UTR_variant	1/49	ENST00000676179.1
KIF1B	NM_183416.4	c.-260C>T		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.-260C>T		5_prime_UTR_variant	1/49		NM_001365951.3	P1
KIF1B	ENST00000377093.9	c.-260C>T		5_prime_UTR_variant	1/21	1
KIF1B	ENST00000696500.1	c.-260C>T		5_prime_UTR_variant, NMD_transcript_variant	1/22

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 269 AN: 151218 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00159

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.000781

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00208

Gnomad OTH AF: 0.00241

GnomAD4 exome AF: 0.0147 AC: 3 AN: 204 Hom.: 0 AF XY: 0.0197 AC XY: 3 AN XY: 152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0172

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00178 AC: 269 AN: 151324 Hom.: 2 Cov.: 32 AF XY: 0.00185 AC XY: 137 AN XY: 73958

Gnomad4 AFR AF: 0.000338

Gnomad4 AMR AF: 0.00159

Gnomad4 ASJ AF: 0.00808

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.000781

Gnomad4 NFE AF: 0.00208

Gnomad4 OTH AF: 0.00239

Alfa AF: 0.00217 Hom.: 1

Bravo AF: 0.00142

Asia WGS AF: 0.00239 AC: 10 AN: 3362

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Pheochromocytoma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neuroblastoma 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.2
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149705989; hg19: chr1-10270756;