Genetic Variant KIF11:c.698+322G>T (chr10-92609831-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004523.4(KIF11):c.698+322G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,998 control chromosomes in the GnomAD database, including 8,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 8230 hom., cov: 31)

Consequence

KIF11
NM_004523.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.305

Publications

4 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 10-92609831-G-T is Benign according to our data. Variant chr10-92609831-G-T is described in ClinVar as Benign. ClinVar VariationId is 1296598.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4 link	c.698+322G>T		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.698+322G>T		intron_variant	Intron 6 of 21	1	NM_004523.4	ENSP00000260731.3		P52732

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47032

AN:

151880

Hom.:

8228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.320

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

GnomAD4 genome

AF:

0.310

AC:

47051

AN:

151998

Hom.:

8230

Cov.:

AF XY:

0.314

AC XY:

23336

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.173

AC:

7162

AN:

41480

American (AMR)

AF:

0.261

AC:

3982

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1231

AN:

3470

East Asian (EAS)

AF:

0.672

AC:

3469

AN:

5160

South Asian (SAS)

AF:

0.469

AC:

2259

AN:

4818

European-Finnish (FIN)

AF:

0.392

AC:

4136

AN:

10548

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.347

AC:

23596

AN:

67956

Other (OTH)

AF:

0.321

AC:

675

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1570

3140

4709

6279

7849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.195

Hom.:

438

Bravo

AF:

0.297

Asia WGS

AF:

0.507

AC:

1759

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 17, 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

-0.96

CADD

Benign

1.2

(source)

DANN

Benign

0.73

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over