dbSNP rs74436006: KIF27:p.Glu1018Glu (chr9-83859252-T-C) – 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.3054A>G(p.Glu1018Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,612,906 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 66 hom., cov: 31)

Exomes 𝑓: 0.014 ( 210 hom. )

Consequence

KIF27
NM_017576.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0390

Publications

1 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 9-83859252-T-C is Benign according to our data. Variant chr9-83859252-T-C is described in ClinVar as Benign. ClinVar VariationId is 403014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.039 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF27	NM_017576.4 link	c.3054A>G	p.Glu1018Glu	synonymous_variant	Exon 14 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.3054A>G	p.Glu1018Glu	synonymous_variant	Exon 14 of 18	1	NM_017576.4	ENSP00000297814.2		Q86VH2-1

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3530

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0527

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.00668

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.0150

AC:

3757

AN:

251290

AF XY:

0.0147

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.00761

Gnomad ASJ exome

AF:

0.0364

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00517

Gnomad NFE exome

AF:

0.0133

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0140

AC:

20485

AN:

1460882

Hom.:

210

Cov.:

AF XY:

0.0143

AC XY:

10406

AN XY:

726778

show subpopulations

African (AFR)

AF:

0.0511

AC:

1685

AN:

32994

American (AMR)

AF:

0.00814

AC:

364

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0359

AC:

937

AN:

26132

East Asian (EAS)

AF:

0.000428

AC:

AN:

39676

South Asian (SAS)

AF:

0.0191

AC:

1647

AN:

86242

European-Finnish (FIN)

AF:

0.00453

AC:

242

AN:

53416

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0130

AC:

14490

AN:

1111618

Other (OTH)

AF:

0.0171

AC:

1031

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

1056

2111

3167

4222

5278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.0232

AC:

3532

AN:

152024

Hom.:

Cov.:

AF XY:

0.0228

AC XY:

1698

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0526

AC:

2175

AN:

41320

American (AMR)

AF:

0.0142

AC:

217

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3470

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.0166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00668

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0120

AC:

817

AN:

68010

Other (OTH)

AF:

0.0180

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

174

347

521

694

868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0193

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0133

EpiControl

AF:

0.0160

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: MAF -

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

3.4

(source)

DANN

Benign

0.78

PhyloP100

-0.039

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