rs172431

Positions:

• chr10-32037109-G-A

Variant summary

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

The NM_004521.3(KIF5B):​c.711+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 661,364 control chromosomes in the GnomAD database, including 16,938 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 (3619 hom., cov: 32)
  • Exomes 𝑓: 0.22 (13319 hom.)
• Consequence: KIF5B NM_004521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.89).
• 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	Protein	UniProt
KIF5B	NM_004521.3	c.711+145C>T		intron_variant		ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.711+145C>T		intron_variant			XP_047281158.1
KIF5B	XM_047425203.1	c.429+145C>T		intron_variant			XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.711+145C>T		intron_variant		1	NM_004521.3	ENSP00000307078.4

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32226 AN: 151934 Hom.: 3610 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00788

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.217 AC: 110471 AN: 509312 Hom.: 13319 AF XY: 0.217 AC XY: 58548 AN XY: 269826

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.00462

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.212 AC: 32273 AN: 152052 Hom.: 3619 Cov.: 32 AF XY: 0.208 AC XY: 15446 AN XY: 74346

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.214

Alfa AF: 0.237 Hom.: 2186

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	-0.89
CADD	Benign	2.4
DANN	Benign	0.47

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: rs172431; hg19: chr10-32326037;