10-32019466-A-C

Variant names:

• chr10-32019466-A-C
• rs2286746
• NM_004521.3:c.2306+392T>G

Variant summary

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

The NM_004521.3(KIF5B):​c.2306+392T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,250 control chromosomes in the GnomAD database, including 1,113 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 0.089 (1113 hom., cov: 33)
• Consequence: KIF5B NM_004521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 6 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]

LOC107984219 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF5B	NM_004521.3	c.2306+392T>G		intron_variant	Intron 20 of 25	ENST00000302418.5	NP_004512.1
LOC107984219	XR_001747415.2	n.6794A>C		non_coding_transcript_exon_variant	Exon 3 of 3
KIF5B	XM_047425202.1	c.2306+392T>G		intron_variant	Intron 20 of 24		XP_047281158.1
KIF5B	XM_047425203.1	c.2024+392T>G		intron_variant	Intron 21 of 26		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.2306+392T>G		intron_variant	Intron 20 of 25	1	NM_004521.3	ENSP00000307078.4
KIF5B	ENST00000493889.1	n.175+392T>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13496 AN: 152132 Hom.: 1116 Cov.: 33

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.0890

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

GnomAD4 genome AF: 0.0886 AC: 13484 AN: 152250 Hom.: 1113 Cov.: 33 AF XY: 0.0961 AC XY: 7150 AN XY: 74432

African (AFR) AF: 0.0189 AC: 787 AN: 41562

American (AMR) AF: 0.103 AC: 1582 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 296 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2414 AN: 5174

South Asian (SAS) AF: 0.165 AC: 795 AN: 4826

European-Finnish (FIN) AF: 0.145 AC: 1532 AN: 10600

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0851 AC: 5790 AN: 68004

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0832 Hom.: 1058

Bravo AF: 0.0837

Asia WGS AF: 0.247 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.9
DANN	Benign	0.78
PhyloP100		0.37
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: rs2286746; hg19: chr10-32308394;