rs4240913

Positions:

• chr1-10377746-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365951.3(KIF1B):​c.*1159G>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 0.102 in 185,554 control chromosomes in the GnomAD database, including 1,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (948 hom., cov: 32)
  • Exomes 𝑓: 0.11 (234 hom.)
• Consequence: KIF1B NM_001365951.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.952

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-10377746-G-A is Benign according to our data. Variant chr1-10377746-G-A is described in ClinVar as [Benign]. Clinvar id is 291608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.*1159G>A		3_prime_UTR_variant	49/49	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1	c.*1159G>A		3_prime_UTR_variant	49/49		NP_001352881.1
KIF1B	NM_015074.3	c.*1159G>A		3_prime_UTR_variant	47/47		NP_055889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.*1159G>A		3_prime_UTR_variant	49/49		NM_001365951.3	ENSP00000502065	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15349 AN: 152062 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.00695

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.109 AC: 3641 AN: 33374 Hom.: 234 Cov.: 0 AF XY: 0.111 AC XY: 1722 AN XY: 15520

Gnomad4 AFR exome AF: 0.0437

Gnomad4 AMR exome AF: 0.0901

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.0159

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.101 AC: 15346 AN: 152180 Hom.: 948 Cov.: 32 AF XY: 0.101 AC XY: 7504 AN XY: 74398

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.0909

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.00697

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.113

Alfa AF: 0.107 Hom.: 128

Bravo AF: 0.0960

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neuroblastoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.70

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: rs4240913; hg19: chr1-10437804;