NM_004521.3:c.214+2226C>T

Variant names:

• chr10-32046238-G-A
• rs211286
• NM_004521.3:c.214+2226C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004521.3(KIF5B):​c.214+2226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,030 control chromosomes in the GnomAD database, including 3,618 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 (3618 hom., cov: 32)
• Consequence: KIF5B NM_004521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• 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 rank	MANE	Protein	UniProt
KIF5B	NM_004521.3	c.214+2226C>T		intron_variant	Intron 2 of 25	ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.214+2226C>T		intron_variant	Intron 2 of 24		XP_047281158.1
KIF5B	XM_047425203.1	c.-69+2226C>T		intron_variant	Intron 3 of 26		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.214+2226C>T		intron_variant	Intron 2 of 25	1	NM_004521.3	ENSP00000307078.4

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32236 AN: 151912 Hom.: 3609 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32283 AN: 152030 Hom.: 3618 Cov.: 32 AF XY: 0.208 AC XY: 15450 AN XY: 74300

African (AFR) AF: 0.203 AC: 8414 AN: 41436

American (AMR) AF: 0.187 AC: 2850 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5180

South Asian (SAS) AF: 0.179 AC: 860 AN: 4814

European-Finnish (FIN) AF: 0.183 AC: 1937 AN: 10582

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16683 AN: 67962

Other (OTH) AF: 0.215 AC: 453 AN: 2110

Alfa AF: 0.117 Hom.: 191

Bravo AF: 0.214

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.23
PhyloP100		-1.3
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: rs211286; hg19: chr10-32335166;