Variant rs1047972 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_198437.3(AURKA):c.169A>G(p.Ile57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,613,986 control chromosomes in the GnomAD database, including 575,145 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.84 ( 54283 hom., cov: 31)

Exomes 𝑓: 0.84 ( 520862 hom. )

Consequence

AURKA
NM_198437.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.556

Variant links:

Genes affected

AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

AURKA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.0621073E-7).

BP6

Variant 20-56386407-T-C is Benign according to our data. Variant chr20-56386407-T-C is described in ClinVar as [Benign]. Clinvar id is 3059051.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3 link	c.169A>G	p.Ile57Val	missense_variant	Exon 3 of 9	ENST00000395915.8	NP_940839.1	O14965

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8 link	c.169A>G	p.Ile57Val	missense_variant	Exon 3 of 9	1	NM_198437.3	ENSP00000379251.3		O14965

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128366

AN:

152010

Hom.:

54229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.838

Gnomad AMI

AF:

0.892

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.881

Gnomad SAS

AF:

0.856

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.860

GnomAD3 exomes

AF:

0.851

AC:

213970

AN:

251486

Hom.:

91168

AF XY:

0.848

AC XY:

115283

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.853

Gnomad EAS exome

AF:

0.878

Gnomad SAS exome

AF:

0.859

Gnomad FIN exome

AF:

0.807

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.842

GnomAD4 exome

AF:

0.844

AC:

1233537

AN:

1461858

Hom.:

520862

Cov.:

AF XY:

0.844

AC XY:

613833

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.834

Gnomad4 AMR exome

AF:

0.912

Gnomad4 ASJ exome

AF:

0.858

Gnomad4 EAS exome

AF:

0.871

Gnomad4 SAS exome

AF:

0.858

Gnomad4 FIN exome

AF:

0.810

Gnomad4 NFE exome

AF:

0.840

Gnomad4 OTH exome

AF:

0.847

GnomAD4 genome

AF:

0.845

AC:

128476

AN:

152128

Hom.:

54283

Cov.:

AF XY:

0.843

AC XY:

62696

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.838

Gnomad4 AMR

AF:

0.887

Gnomad4 ASJ

AF:

0.865

Gnomad4 EAS

AF:

0.880

Gnomad4 SAS

AF:

0.855

Gnomad4 FIN

AF:

0.810

Gnomad4 NFE

AF:

0.838

Gnomad4 OTH

AF:

0.856

Alfa

AF:

0.838

Hom.:

136903

Bravo

AF:

0.850

TwinsUK

AF:

0.841

AC:

3119

ALSPAC

AF:

0.847

AC:

3265

ESP6500AA

AF:

0.838

AC:

3693

ESP6500EA

AF:

0.838

AC:

7203

ExAC

AF:

0.848

AC:

102977

Asia WGS

AF:

0.872

AC:

3034

AN:

3478

EpiCase

AF:

0.829

EpiControl

AF:

0.826

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AURKA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.032

DANN

Benign

0.21

DEOGEN2

Benign

0.0047

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.016

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

MetaRNN

Benign

6.1e-7

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

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.010

N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.031

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

.;.;.;.;.;.;.;B;B;B;B;B;.

Vest4

0.010

ClinPred

0.00020

GERP RS

2.0

gMVP

0.092

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