rs4646953

Positions:

• chr10-92574198-A-G

Variant summary

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

The ENST00000676757.1(KIF11):​c.-131+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 550,568 control chromosomes in the GnomAD database, including 10,220 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 0.17 (2434 hom., cov: 33)
  • Exomes 𝑓: 0.19 (7786 hom.)
• Consequence: KIF11 ENST00000676757.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

Genes affected

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.92574198A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000676757.1	c.-131+5A>G		splice_region_variant, intron_variant				ENSP00000504289.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25124 AN: 152020 Hom.: 2434 Cov.: 33

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0460

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.187 AC: 74490 AN: 398430 Hom.: 7786 AF XY: 0.184 AC XY: 38573 AN XY: 209426

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.0293

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.165 AC: 25120 AN: 152138 Hom.: 2434 Cov.: 33 AF XY: 0.167 AC XY: 12454 AN XY: 74374

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.0457

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.169

Alfa AF: 0.183 Hom.: 349

Bravo AF: 0.153

Asia WGS AF: 0.113 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4646953; hg19: chr10-94333955;