dbSNP rs2275220: KIF11:c.699-91A>G (chr10-92612949-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004523.4(KIF11):c.699-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 700,048 control chromosomes in the GnomAD database, including 639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 138 hom., cov: 32)

Exomes 𝑓: 0.039 ( 501 hom. )

Consequence

KIF11
NM_004523.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.306

Publications

5 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=-0.78).

BP6

Variant 10-92612949-A-G is Benign according to our data. Variant chr10-92612949-A-G is described in ClinVar as Benign. ClinVar VariationId is 1245602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4 link	c.699-91A>G		intron_variant	Intron 6 of 21	ENST00000260731.5	NP_004514.2	P52732

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5 link	c.699-91A>G		intron_variant	Intron 6 of 21	1	NM_004523.4	ENSP00000260731.3		P52732

Frequencies

GnomAD3 genomes

AF:

0.0338

AC:

5141

AN:

152084

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00910

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0605

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.0308

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.0815

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0388

Gnomad OTH

AF:

0.0225

GnomAD4 exome

AF:

0.0392

AC:

21454

AN:

547846

Hom.:

501

AF XY:

0.0376

AC XY:

10848

AN XY:

288894

show subpopulations

African (AFR)

AF:

0.0100

AC:

143

AN:

14276

American (AMR)

AF:

0.0759

AC:

1638

AN:

21580

Ashkenazi Jewish (ASJ)

AF:

0.0139

AC:

205

AN:

14776

East Asian (EAS)

AF:

0.0252

AC:

814

AN:

32340

South Asian (SAS)

AF:

0.0177

AC:

825

AN:

46556

European-Finnish (FIN)

AF:

0.0792

AC:

3555

AN:

44882

Middle Eastern (MID)

AF:

0.00561

AC:

AN:

2316

European-Non Finnish (NFE)

AF:

0.0387

AC:

13249

AN:

342098

Other (OTH)

AF:

0.0349

AC:

1012

AN:

29022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

991

1982

2973

3964

4955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0338

AC:

5139

AN:

152202

Hom.:

138

Cov.:

AF XY:

0.0357

AC XY:

2655

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00908

AC:

377

AN:

41536

American (AMR)

AF:

0.0603

AC:

922

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3468

East Asian (EAS)

AF:

0.0307

AC:

159

AN:

5178

South Asian (SAS)

AF:

0.0149

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0815

AC:

863

AN:

10590

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0388

AC:

2641

AN:

68012

Other (OTH)

AF:

0.0223

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

249

498

748

997

1246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0365

Hom.:

209

Bravo

AF:

0.0305

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 31, 2018

GeneDx

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

-0.78

CADD

Benign

6.0

(source)

DANN

Benign

0.72

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism

(source)

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

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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