rs172431

Variant names:

• chr10-32037109-G-A
• rs172431
• NM_004521.3:c.711+145C>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.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
• Publications: 8 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=-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 rank	MANE	Protein	UniProt
KIF5B	NM_004521.3	c.711+145C>T		intron_variant	Intron 8 of 25	ENST00000302418.5	NP_004512.1
KIF5B	XM_047425202.1	c.711+145C>T		intron_variant	Intron 8 of 24		XP_047281158.1
KIF5B	XM_047425203.1	c.429+145C>T		intron_variant	Intron 9 of 26		XP_047281159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5B	ENST00000302418.5	c.711+145C>T		intron_variant	Intron 8 of 25	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

African (AFR) AF: 0.199 AC: 2676 AN: 13466

American (AMR) AF: 0.195 AC: 3612 AN: 18532

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 3300 AN: 14056

East Asian (EAS) AF: 0.00462 AC: 146 AN: 31596

South Asian (SAS) AF: 0.201 AC: 9560 AN: 47626

European-Finnish (FIN) AF: 0.190 AC: 6756 AN: 35636

Middle Eastern (MID) AF: 0.295 AC: 609 AN: 2064

European-Non Finnish (NFE) AF: 0.245 AC: 77897 AN: 318434

Other (OTH) AF: 0.212 AC: 5915 AN: 27902

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

African (AFR) AF: 0.203 AC: 8419 AN: 41454

American (AMR) AF: 0.186 AC: 2845 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3468

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5188

South Asian (SAS) AF: 0.179 AC: 861 AN: 4820

European-Finnish (FIN) AF: 0.183 AC: 1932 AN: 10564

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

European-Non Finnish (NFE) AF: 0.245 AC: 16681 AN: 67970

Other (OTH) AF: 0.214 AC: 451 AN: 2108

Alfa AF: 0.237 Hom.: 2447

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
PhyloP100		-0.042
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: rs172431; hg19: chr10-32326037;