rs72811230

chr10-92648450-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004523.4(KIF11):c.2770+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 1,492,596 control chromosomes in the GnomAD database, including 4,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (288 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3752 hom.)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.29

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-92648450-A-G is Benign according to our data. Variant chr10-92648450-A-G is described in ClinVar as [Benign]. Clinvar id is 259410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92648450-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF11	NM_004523.4	c.2770+16A>G		intron_variant		ENST00000260731.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF11	ENST00000260731.5	c.2770+16A>G		intron_variant		1	NM_004523.4	P1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8007 AN: 152190 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.0546

GnomAD3 exomes AF: 0.0582 AC: 11805 AN: 202986 Hom.: 432 AF XY: 0.0587 AC XY: 6486 AN XY: 110538

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.0385

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.000129

Gnomad SAS exome AF: 0.0204

Gnomad FIN exome AF: 0.0985

Gnomad NFE exome AF: 0.0742

Gnomad OTH exome AF: 0.0696

GnomAD4 exome AF: 0.0696 AC: 93218 AN: 1340286 Hom.: 3752 Cov.: 19 AF XY: 0.0682 AC XY: 45576 AN XY: 668118

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.0406

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0000795

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.0936

Gnomad4 NFE exome AF: 0.0767

Gnomad4 OTH exome AF: 0.0633

GnomAD4 genome AF: 0.0525 AC: 8003 AN: 152310 Hom.: 288 Cov.: 32 AF XY: 0.0533 AC XY: 3969 AN XY: 74474

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0492

Gnomad4 ASJ AF: 0.0952

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0735

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0642 Hom.: 76

Bravo AF: 0.0482

Asia WGS AF: 0.00837 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.87

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: rs72811230; hg19: chr10-94408207;