dbSNP rs149651741: AURKB:p.Gly212Arg (chr17-8206543-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

Variant links:

COSMIC-nc: COSV104412340

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 was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 931197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 150 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004217.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AURKB	NM_004217.4	MANE Select	c.634G>C	p.Gly212Arg	missense	Exon 7 of 9	NP_004208.2	Q96GD4-1
AURKB	NM_001284526.2		c.637G>C	p.Gly213Arg	missense	Exon 7 of 9	NP_001271455.1	Q96GD4-5
AURKB	NM_001313950.2		c.634G>C	p.Gly212Arg	missense	Exon 7 of 9	NP_001300879.1	Q96GD4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AURKB	ENST00000585124.6	TSL:1 MANE Select	c.634G>C	p.Gly212Arg	missense	Exon 7 of 9	ENSP00000463999.1	Q96GD4-1
AURKB	ENST00000316199.10	TSL:1	c.637G>C	p.Gly213Arg	missense	Exon 7 of 9	ENSP00000313950.6	Q96GD4-5
AURKB	ENST00000578549.5	TSL:1	c.538G>C	p.Gly180Arg	missense	Exon 6 of 8	ENSP00000462207.1	Q96GD4-2

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

GnomAD2 exomes

AF:

0.000958

AC:

241

AN:

251450

AF XY:

0.000957

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 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

African (AFR)

AF:

0.000568

AC:

AN:

33480

American (AMR)

AF:

0.000894

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00144

AC:

124

AN:

86258

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00146

AC:

1621

AN:

1112012

Other (OTH)

AF:

0.000944

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

121

241

362

482

603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.000985

AC:

150

AN:

152306

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41574

American (AMR)

AF:

0.00131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00147

AC:

100

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00106

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.035

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

PhyloP100

7.9

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-7.4

REVEL

Uncertain

0.51

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.010

Polyphen

0.94

Vest4

0.88

MutPred

0.67

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

Mutation Taster

=35/65

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over