1-10210657-GCC-G

Variant names:

• chr1-10210657-GCC-G
• rs140167753
• NM_001365951.3:c.-299_-298delCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001365951.3(KIF1B):​c.-299_-298delCC 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
• 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 -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 rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.-299_-298delCC		5_prime_UTR_variant	Exon 1 of 49	ENST00000676179.1	NP_001352880.1
KIF1B	NM_183416.4	c.-299_-298delCC		5_prime_UTR_variant	Exon 1 of 21		NP_904325.2
KIF1B	NM_015074.3	c.-300_-299delCC		upstream_gene_variant			NP_055889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.-299_-298delCC		5_prime_UTR_variant	Exon 1 of 49		NM_001365951.3	ENSP00000502065.1

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

African (AFR) AF: 0.250 AC: 3 AN: 12

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2 AN: 10

East Asian (EAS) AF: 0.250 AC: 6 AN: 24

South Asian (SAS) AF: 0.0556 AC: 1 AN: 18

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.186 AC: 135 AN: 724

Other (OTH) AF: 0.289 AC: 11 AN: 38

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

African (AFR) AF: 0.167 AC: 6904 AN: 41438

American (AMR) AF: 0.309 AC: 4694 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 889 AN: 3462

East Asian (EAS) AF: 0.291 AC: 1493 AN: 5136

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4820

European-Finnish (FIN) AF: 0.260 AC: 2696 AN: 10352

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.274 AC: 18572 AN: 67714

Other (OTH) AF: 0.260 AC: 545 AN: 2098

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

Jun 22, 2018

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		0.24

Splicing

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

Other links and lift over

dbSNP: rs140167753; hg19: chr1-10270715;