rs75876570

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004523.4(KIF11):c.2771-6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,588,138 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 40 hom. )

Consequence

KIF11
NM_004523.4 splice_region, intron

Scores

Splicing: ADA: 0.04179

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.160

Publications

3 publications found

Variant links:

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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

KIF11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-92649829-T-A is Benign according to our data. Variant chr10-92649829-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 211273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00546 (7845/1435868) while in subpopulation MID AF = 0.0183 (104/5684). AF 95% confidence interval is 0.0154. There are 40 homozygotes in GnomAdExome4. There are 3921 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High AC in GnomAd4 at 682 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4 link	c.2771-6T>A		splice_region_variant, intron_variant	Intron 19 of 21	ENST00000260731.5	NP_004514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5 link	c.2771-6T>A		splice_region_variant, intron_variant	Intron 19 of 21	1	NM_004523.4	ENSP00000260731.3

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

682

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00583

Gnomad OTH

AF:

0.00812

GnomAD2 exomes

AF:

0.00494

AC:

1219

AN:

246914

AF XY:

0.00528

show subpopulations

Gnomad AFR exome

AF:

0.000807

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.00657

Gnomad OTH exome

AF:

0.00632

GnomAD4 exome

AF:

0.00546

AC:

7845

AN:

1435868

Hom.:

Cov.:

AF XY:

0.00551

AC XY:

3921

AN XY:

711722

show subpopulations

African (AFR)

AF:

0.00112

AC:

AN:

32932

American (AMR)

AF:

0.00450

AC:

195

AN:

43288

Ashkenazi Jewish (ASJ)

AF:

0.0139

AC:

355

AN:

25586

East Asian (EAS)

AF:

0.00

AC:

AN:

39306

South Asian (SAS)

AF:

0.00448

AC:

373

AN:

83194

European-Finnish (FIN)

AF:

0.000888

AC:

AN:

52926

Middle Eastern (MID)

AF:

0.0183

AC:

104

AN:

5684

European-Non Finnish (NFE)

AF:

0.00578

AC:

6322

AN:

1093672

Other (OTH)

AF:

0.00695

AC:

412

AN:

59280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

334

668

1001

1335

1669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00448

AC:

682

AN:

152270

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

41534

American (AMR)

AF:

0.00797

AC:

122

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00436

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000661

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00584

AC:

397

AN:

68034

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00701

Hom.:

Bravo

AF:

0.00451

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF11: BP4, BS2 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 11, 2015

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

(source)

DANN

Benign

0.46

PhyloP100

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.042

dbscSNV1_RF

Benign

0.42

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over