1-10232301-CAT-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001365951.3(KIF1B):​c.-16_-15delTA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,256,448 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF1B NM_001365951.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 1-10232301-CAT-C is Benign according to our data. Variant chr1-10232301-CAT-C is described in ClinVar as [Benign]. Clinvar id is 1251192.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151308 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00107 AC: 206 AN: 192740 AF XY: 0.00109

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.000712

Gnomad ASJ exome AF: 0.00132

Gnomad EAS exome AF: 0.000275

Gnomad FIN exome AF: 0.00142

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000623

GnomAD4 exome AF: 0.00153 AC: 1922 AN: 1256448 Hom.: 0 AF XY: 0.00143 AC XY: 900 AN XY: 631278

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00143 AC: 42 AN: 29372

American (AMR) AF: 0.000505 AC: 21 AN: 41592

Ashkenazi Jewish (ASJ) AF: 0.000958 AC: 23 AN: 24010

East Asian (EAS) AF: 0.000401 AC: 15 AN: 37360

South Asian (SAS) AF: 0.000584 AC: 46 AN: 78778

European-Finnish (FIN) AF: 0.000870 AC: 44 AN: 50572

Middle Eastern (MID) AF: 0.000559 AC: 3 AN: 5368

European-Non Finnish (NFE) AF: 0.00177 AC: 1661 AN: 936260

Other (OTH) AF: 0.00126 AC: 67 AN: 53136

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151308 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73852

African (AFR) AF: 0.00 AC: 0 AN: 41212

American (AMR) AF: 0.00 AC: 0 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67800

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00800 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=298/2	polymorphism

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

Other links and lift over

dbSNP: rs34063243; hg19: chr1-10292359; COSMIC: COSV55808285; COSMIC: COSV55808285;