rs398686

chr10-32032567-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004521.3(KIF5B):c.1374+139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 674,742 control chromosomes in the GnomAD database, including 17,201 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3616 hom., cov: 32)
  • Exomes 𝑓: 0.22 (13585 hom.)
• Consequence: KIF5B NM_004521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

Genes affected

KIF5B (HGNC:6324): (kinesin family member 5B) Enables identical protein binding activity; microtubule binding activity; and microtubule motor activity. Involved in several processes, including lysosome localization; natural killer cell mediated cytotoxicity; and positive regulation of protein localization to plasma membrane. Located in centriolar satellite; cytosol; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5B	NM_004521.3	c.1374+139G>A		intron_variant		ENST00000302418.5
KIF5B	XM_047425202.1	c.1374+139G>A		intron_variant
KIF5B	XM_047425203.1	c.1092+139G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5B	ENST00000302418.5	c.1374+139G>A		intron_variant		1	NM_004521.3	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32230 AN: 151966 Hom.: 3607 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.216 AC: 113092 AN: 522658 Hom.: 13585 AF XY: 0.217 AC XY: 60792 AN XY: 279910

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.00469

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.212 AC: 32277 AN: 152084 Hom.: 3616 Cov.: 32 AF XY: 0.208 AC XY: 15439 AN XY: 74330

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.00772

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.214

Alfa AF: 0.227 Hom.: 476

Bravo AF: 0.214

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.91
Dann	Benign	0.40

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: rs398686; hg19: chr10-32321495;