NM_001365951.3:c.-16_-15dupTA

Variant names:

• chr1-10232301-C-CAT
• rs34063243
• NM_001365951.3:c.-16_-15dupTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001365951.3(KIF1B):​c.-16_-15dupTA 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 1 publications found

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]

KIF1B Gene-Disease associations (from GenCC):

• pheochromocytoma

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 2A1

  Inheritance: AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neuroblastoma, susceptibility to, 1

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 937 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.-16_-15dupTA		5_prime_UTR_variant	Exon 2 of 49	ENST00000676179.1	NP_001352880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.-16_-15dupTA		5_prime_UTR_variant	Exon 2 of 49		NM_001365951.3	ENSP00000502065.1

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

GnomAD2 exomes AF: 0.00361 AC: 695 AN: 192740 AF XY: 0.00301

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 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

African (AFR) AF: 0.0165 AC: 491 AN: 29836

American (AMR) AF: 0.00213 AC: 91 AN: 42734

Ashkenazi Jewish (ASJ) AF: 0.000530 AC: 13 AN: 24526

East Asian (EAS) AF: 0.00866 AC: 332 AN: 38324

South Asian (SAS) AF: 0.00203 AC: 163 AN: 80442

European-Finnish (FIN) AF: 0.000135 AC: 7 AN: 51808

Middle Eastern (MID) AF: 0.00789 AC: 43 AN: 5448

European-Non Finnish (NFE) AF: 0.00125 AC: 1187 AN: 950522

Other (OTH) AF: 0.00345 AC: 187 AN: 54180

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

African (AFR) AF: 0.0175 AC: 722 AN: 41336

American (AMR) AF: 0.00389 AC: 59 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.0126 AC: 65 AN: 5174

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000944 AC: 64 AN: 67802

Other (OTH) AF: 0.00764 AC: 16 AN: 2094

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00678

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Neuroblastoma Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pheochromocytoma Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 2 Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs34063243; hg19: chr1-10292359; COSMIC: COSV55803930; COSMIC: COSV55803930;