Genetic Variant KIF27:p.Ile1062Ile (chr9-83853800-A-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017576.4(KIF27):c.3186T>A(p.Ile1062Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,611,514 control chromosomes in the GnomAD database, including 338,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35243 hom., cov: 31)

Exomes 𝑓: 0.64 ( 303325 hom. )

Consequence

KIF27
NM_017576.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.594

Publications

18 publications found

Variant links:

Genes affected

KIF27 (HGNC:18632): (kinesin family member 27) This gene is a member of the KIF27 (kinesin 4) sub-family of the mammalian kinesin family. The gene is an ortholog of the Drosophila Cos2 gene, which plays an important role in the Hedgehog signaling pathway. The encoded protein contains an N-terminal motor domain which includes nucleotide-binding and microtubule-interacting regions, a stalk domain containing a predicted coiled coil motif and a C-terminal tail domain. Alternatively spliced transcript variants have been observed for this gene. Pseudogenes associated with this gene are located on chromosome 9. [provided by RefSeq, Dec 2012]

KIF27 links:

ENSG00000226877 (HGNC:):

ENSG00000226877 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 9-83853800-A-T is Benign according to our data. Variant chr9-83853800-A-T is described in ClinVar as Benign. ClinVar VariationId is 403012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.594 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF27	NM_017576.4 link	c.3186T>A	p.Ile1062Ile	synonymous_variant	Exon 15 of 18	ENST00000297814.7	NP_060046.1	Q86VH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF27	ENST00000297814.7 link	c.3186T>A	p.Ile1062Ile	synonymous_variant	Exon 15 of 18	1	NM_017576.4	ENSP00000297814.2		Q86VH2-1

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

102257

AN:

151916

Hom.:

35181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.802

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.648

GnomAD2 exomes

AF:

0.620

AC:

155598

AN:

250842

AF XY:

0.628

show subpopulations

Gnomad AFR exome

AF:

0.806

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.650

Gnomad EAS exome

AF:

0.506

Gnomad FIN exome

AF:

0.693

Gnomad NFE exome

AF:

0.651

Gnomad OTH exome

AF:

0.621

GnomAD4 exome

AF:

0.642

AC:

936623

AN:

1459480

Hom.:

303325

Cov.:

AF XY:

0.642

AC XY:

466563

AN XY:

726214

show subpopulations

African (AFR)

AF:

0.813

AC:

27200

AN:

33436

American (AMR)

AF:

0.419

AC:

18745

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.644

AC:

16804

AN:

26110

East Asian (EAS)

AF:

0.531

AC:

21077

AN:

39668

South Asian (SAS)

AF:

0.661

AC:

56949

AN:

86216

European-Finnish (FIN)

AF:

0.699

AC:

37299

AN:

53394

Middle Eastern (MID)

AF:

0.641

AC:

3689

AN:

5752

European-Non Finnish (NFE)

AF:

0.645

AC:

715888

AN:

1109890

Other (OTH)

AF:

0.646

AC:

38972

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

16009

32019

48028

64038

80047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18794

37588

56382

75176

93970

<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:

0.673

AC:

102378

AN:

152034

Hom.:

35243

Cov.:

AF XY:

0.672

AC XY:

49949

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.803

AC:

33312

AN:

41506

American (AMR)

AF:

0.519

AC:

7920

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2220

AN:

3466

East Asian (EAS)

AF:

0.519

AC:

2676

AN:

5158

South Asian (SAS)

AF:

0.638

AC:

3068

AN:

4808

European-Finnish (FIN)

AF:

0.694

AC:

7328

AN:

10560

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.644

AC:

43762

AN:

67948

Other (OTH)

AF:

0.651

AC:

1374

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1649

3297

4946

6594

8243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.631

Hom.:

8041

Bravo

AF:

0.663

Asia WGS

AF:

0.595

AC:

2068

AN:

3478

EpiCase

AF:

0.641

EpiControl

AF:

0.646

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.2

(source)

DANN

Benign

0.78

PhyloP100

0.59

Mutation Taster

=100/0

polymorphism (auto)

(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