rs3748578

Variant names:

• chr1-10360860-G-A
• rs3748578
• NM_001365951.3:c.4056-69G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-10360860-G-A
• chr1-10360860-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365951.3(KIF1B):​c.4056-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 992,654 control chromosomes in the GnomAD database, including 44,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6599 hom., cov: 31)
  • Exomes 𝑓: 0.30 (37709 hom.)
• Consequence: KIF1B NM_001365951.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.694
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-10360860-G-A is Benign according to our data. Variant chr1-10360860-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1B	NM_001365951.3	c.4056-69G>A		intron_variant	Intron 38 of 48	ENST00000676179.1	NP_001352880.1
KIF1B	NM_001365952.1	c.4056-69G>A		intron_variant	Intron 38 of 48		NP_001352881.1
KIF1B	NM_015074.3	c.3918-69G>A		intron_variant	Intron 36 of 46		NP_055889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1B	ENST00000676179.1	c.4056-69G>A		intron_variant	Intron 38 of 48		NM_001365951.3	ENSP00000502065.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44370 AN: 151914 Hom.: 6576 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.298 AC: 250510 AN: 840622 Hom.: 37709 AF XY: 0.295 AC XY: 130807 AN XY: 443696

African (AFR) AF: 0.274 AC: 5854 AN: 21372

American (AMR) AF: 0.349 AC: 15188 AN: 43510

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 6233 AN: 22300

East Asian (EAS) AF: 0.251 AC: 9257 AN: 36898

South Asian (SAS) AF: 0.235 AC: 17319 AN: 73754

European-Finnish (FIN) AF: 0.303 AC: 16069 AN: 53016

Middle Eastern (MID) AF: 0.209 AC: 964 AN: 4606

European-Non Finnish (NFE) AF: 0.308 AC: 167839 AN: 545162

Other (OTH) AF: 0.295 AC: 11787 AN: 40004

GnomAD4 genome AF: 0.292 AC: 44443 AN: 152032 Hom.: 6599 Cov.: 31 AF XY: 0.293 AC XY: 21734 AN XY: 74304

African (AFR) AF: 0.271 AC: 11239 AN: 41436

American (AMR) AF: 0.337 AC: 5153 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 942 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5170

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4828

European-Finnish (FIN) AF: 0.295 AC: 3113 AN: 10564

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20272 AN: 67962

Other (OTH) AF: 0.293 AC: 620 AN: 2114

Alfa AF: 0.298 Hom.: 17485

Bravo AF: 0.296

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.64
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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: rs3748578; hg19: chr1-10420918; COSMIC: COSV55805417; COSMIC: COSV55805417;