10-92608421-G-A

Variant names:

• chr10-92608421-G-A
• rs11187094
• NM_004523.4:c.388-599G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004523.4(KIF11):​c.388-599G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,702 control chromosomes in the GnomAD database, including 4,019 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 0.20 (4019 hom., cov: 31)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 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.388-599G>A		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.388-599G>A		intron	N/A	ENSP00000260731.3	P52732
	KIF11	ENST00000937278.1		c.388-599G>A		intron	N/A	ENSP00000607337.1
	KIF11	ENST00000676647.1		c.181-599G>A		intron	N/A	ENSP00000503394.1	A0A7I2V3A9

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30114 AN: 151590 Hom.: 4023 Cov.: 31

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.198 AC: 30107 AN: 151702 Hom.: 4019 Cov.: 31 AF XY: 0.206 AC XY: 15297 AN XY: 74114

African (AFR) AF: 0.0609 AC: 2511 AN: 41244

American (AMR) AF: 0.173 AC: 2633 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.591 AC: 3046 AN: 5154

South Asian (SAS) AF: 0.426 AC: 2054 AN: 4826

European-Finnish (FIN) AF: 0.281 AC: 2946 AN: 10484

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15190 AN: 67960

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.205 Hom.: 9384

Bravo AF: 0.185

Asia WGS AF: 0.450 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.63
DANN	Benign	0.68
PhyloP100		-0.95
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: rs11187094; hg19: chr10-94368178;