rs211299

Positions:

• chr10-32055819-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.126+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,608,032 control chromosomes in the GnomAD database, including 11,109 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 0.095 (794 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10315 hom.)
• Consequence: KIF5B NM_004521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5B	NM_004521.3	c.126+29C>T		intron_variant		ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.126+29C>T		intron_variant			XP_047281158.1
KIF5B	XM_047425203.1	c.-371+29C>T		intron_variant			XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.126+29C>T		intron_variant		1	NM_004521.3	ENSP00000307078.4

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14384 AN: 152128 Hom.: 794 Cov.: 33

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0870

GnomAD3 exomes AF: 0.0991 AC: 24389 AN: 246108 Hom.: 1459 AF XY: 0.106 AC XY: 14150 AN XY: 133608

Gnomad AFR exome AF: 0.0619

Gnomad AMR exome AF: 0.0415

Gnomad ASJ exome AF: 0.0949

Gnomad EAS exome AF: 0.00120

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.115 AC: 166935 AN: 1455786 Hom.: 10315 Cov.: 32 AF XY: 0.116 AC XY: 84235 AN XY: 723862

Gnomad4 AFR exome AF: 0.0657

Gnomad4 AMR exome AF: 0.0440

Gnomad4 ASJ exome AF: 0.0914

Gnomad4 EAS exome AF: 0.000606

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0945 AC: 14389 AN: 152246 Hom.: 794 Cov.: 33 AF XY: 0.0947 AC XY: 7049 AN XY: 74436

Gnomad4 AFR AF: 0.0658

Gnomad4 AMR AF: 0.0614

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0861

Alfa AF: 0.106 Hom.: 175

Bravo AF: 0.0887

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.91

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: rs211299; hg19: chr10-32344747; COSMIC: COSV56657279; COSMIC: COSV56657279;