chr17-8206543-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP3BP4_ModerateBP6_Very_StrongBS2

The NM_004217.4(AURKB):c.634G>C(p.Gly212Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,192 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

AURKB
NM_004217.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.89

Variant links:

Genes affected

AURKB (HGNC:11390): (aurora kinase B) This gene encodes a member of the aurora kinase subfamily of serine/threonine kinases. The genes encoding the other two members of this subfamily are located on chromosomes 19 and 20. These kinases participate in the regulation of alignment and segregation of chromosomes during mitosis and meiosis through association with microtubules. A pseudogene of this gene is located on chromosome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

AURKB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, phyloP100way_vertebrate, PrimateAI, PROVEAN [when max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.24397597).

BP6

Variant 17-8206543-C-G is Benign according to our data. Variant chr17-8206543-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 931197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKB	NM_004217.4 link	c.634G>C	p.Gly212Arg	missense_variant	Exon 7 of 9	ENST00000585124.6	NP_004208.2	Q96GD4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKB	ENST00000585124.6 link	c.634G>C	p.Gly212Arg	missense_variant	Exon 7 of 9	1	NM_004217.4	ENSP00000463999.1		Q96GD4-1

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000958

AC:

241

AN:

251450

Hom.:

AF XY:

0.000957

AC XY:

130

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00129

AC:

1890

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

946

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.00146

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152306

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.000903

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000815

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00113

ClinVar

Significance: Benign/Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 26, 2018

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2,PP3. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.36

.;.;T;.;.;T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.24

T;T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

.;.;M;.;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-7.4

.;D;.;.;.;.;.

REVEL

Uncertain

0.51

Sift

Uncertain

0.0070

.;D;.;.;.;.;.

Sift4G

Uncertain

0.010

D;D;D;D;.;.;D

Polyphen

0.94

.;.;P;.;.;.;.

Vest4

0.88

MutPred

0.67

.;.;Loss of ubiquitination at K211 (P = 0.0455);.;.;Loss of ubiquitination at K211 (P = 0.0455);.;

MVP

0.95

MPC

0.83

ClinPred

0.093

GERP RS

5.5

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.82

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over