rs12259474

Variant names:

• chr10-92607141-A-G
• rs12259474
• NM_004523.4:c.309-18A>G

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: 1.09
• Publications: 6 publications found

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]

KIF11 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 259411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004523.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	NM_004523.4	MANE Select	c.309-18A>G		intron	N/A	NP_004514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	ENST00000260731.5	TSL:1 MANE Select	c.309-18A>G		intron	N/A	ENSP00000260731.3	P52732
	KIF11	ENST00000937278.1		c.309-18A>G		intron	N/A	ENSP00000607337.1
	KIF11	ENST00000676647.1		c.102-18A>G		intron	N/A	ENSP00000503394.1	A0A7I2V3A9

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

GnomAD2 exomes AF: 0.0522 AC: 12910 AN: 247138 AF XY: 0.0466

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 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

African (AFR) AF: 0.412 AC: 12768 AN: 30972

American (AMR) AF: 0.0342 AC: 1494 AN: 43670

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 863 AN: 25378

East Asian (EAS) AF: 0.0475 AC: 1857 AN: 39102

South Asian (SAS) AF: 0.0574 AC: 4775 AN: 83172

European-Finnish (FIN) AF: 0.00278 AC: 148 AN: 53194

Middle Eastern (MID) AF: 0.0835 AC: 439 AN: 5260

European-Non Finnish (NFE) AF: 0.0172 AC: 17395 AN: 1009830

Other (OTH) AF: 0.0511 AC: 2887 AN: 56476

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

African (AFR) AF: 0.392 AC: 16261 AN: 41462

American (AMR) AF: 0.0694 AC: 1060 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3468

East Asian (EAS) AF: 0.0527 AC: 273 AN: 5178

South Asian (SAS) AF: 0.0640 AC: 309 AN: 4828

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0178 AC: 1212 AN: 68024

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.0732 Hom.: 326

Bravo AF: 0.144

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.67
PhyloP100		1.1
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: rs12259474; hg19: chr10-94366898;