10-32056417-T-C

Position:

• chr10-32056417-T-C

Variant summary

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

The NM_004521.3(KIF5B):​c.-444A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 162,730 control chromosomes in the GnomAD database, including 5,492 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 0.26 (5251 hom., cov: 33)
  • Exomes 𝑓: 0.18 (241 hom.)
• Consequence: KIF5B NM_004521.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5B	NM_004521.3	c.-444A>G		5_prime_UTR_variant	1/26	ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.-444A>G		5_prime_UTR_variant	1/25		XP_047281158.1
KIF5B	XM_047425203.1	c.-940A>G		5_prime_UTR_variant	1/27		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.-444A>G		5_prime_UTR_variant	1/26	1	NM_004521.3	ENSP00000307078.4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39475 AN: 151932 Hom.: 5244 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.177 AC: 1888 AN: 10682 Hom.: 241 Cov.: 0 AF XY: 0.184 AC XY: 1058 AN XY: 5762

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.260 AC: 39493 AN: 152048 Hom.: 5251 Cov.: 33 AF XY: 0.261 AC XY: 19408 AN XY: 74332

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.265

Alfa AF: 0.139 Hom.: 256

Bravo AF: 0.264

Asia WGS AF: 0.346 AC: 1204 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
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: rs12251445; hg19: chr10-32345345; COSMIC: COSV56656531; COSMIC: COSV56656531;