rs12259474

chr10-92607141-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.309-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 1,499,214 control chromosomes in the GnomAD database, including 6,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (3362 hom., cov: 32)
  • Exomes 𝑓: 0.032 (3358 hom.)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.09

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=-0.85).
• BP6: Variant 10-92607141-A-G is Benign according to our data. Variant chr10-92607141-A-G is described in ClinVar as [Benign]. Clinvar id is 259411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-92607141-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF11	NM_004523.4	c.309-18A>G		intron_variant		ENST00000260731.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF11	ENST00000260731.5	c.309-18A>G		intron_variant		1	NM_004523.4	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19514 AN: 152042 Hom.: 3356 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.0522 AC: 12910 AN: 247138 Hom.: 1465 AF XY: 0.0466 AC XY: 6239 AN XY: 133760

Gnomad AFR exome AF: 0.401

Gnomad AMR exome AF: 0.0316

Gnomad ASJ exome AF: 0.0319

Gnomad EAS exome AF: 0.0601

Gnomad SAS exome AF: 0.0550

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0387

GnomAD4 exome AF: 0.0316 AC: 42626 AN: 1347054 Hom.: 3358 Cov.: 20 AF XY: 0.0314 AC XY: 21259 AN XY: 676514

Gnomad4 AFR exome AF: 0.412

Gnomad4 AMR exome AF: 0.0342

Gnomad4 ASJ exome AF: 0.0340

Gnomad4 EAS exome AF: 0.0475

Gnomad4 SAS exome AF: 0.0574

Gnomad4 FIN exome AF: 0.00278

Gnomad4 NFE exome AF: 0.0172

Gnomad4 OTH exome AF: 0.0511

GnomAD4 genome AF: 0.128 AC: 19548 AN: 152160 Hom.: 3362 Cov.: 32 AF XY: 0.124 AC XY: 9222 AN XY: 74404

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.0694

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.0527

Gnomad4 SAS AF: 0.0640

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0642 Hom.: 255

Bravo AF: 0.144

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.5
Dann	Benign	0.67

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: rs12259474; hg19: chr10-94366898;