dbSNP rs6092309: AURKA:c.43-128C>T (chr20-56386661-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198437.3(AURKA):c.43-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,075,078 control chromosomes in the GnomAD database, including 421 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 278 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 143 hom. )

Consequence

AURKA
NM_198437.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.519

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

breast cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

AURKA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3 link	c.43-128C>T		intron_variant	Intron 2 of 8	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8 link	c.43-128C>T		intron_variant	Intron 2 of 8	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4845

AN:

152184

Hom.:

279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0173

GnomAD4 exome

AF:

0.00342

AC:

3160

AN:

922776

Hom.:

143

AF XY:

0.00285

AC XY:

1349

AN XY:

472518

show subpopulations

African (AFR)

AF:

0.115

AC:

2520

AN:

21860

American (AMR)

AF:

0.00672

AC:

224

AN:

33314

Ashkenazi Jewish (ASJ)

AF:

0.0000488

AC:

AN:

20480

East Asian (EAS)

AF:

0.00

AC:

AN:

34204

South Asian (SAS)

AF:

0.000289

AC:

AN:

65854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36512

Middle Eastern (MID)

AF:

0.00786

AC:

AN:

4454

European-Non Finnish (NFE)

AF:

0.000137

AC:

AN:

663782

Other (OTH)

AF:

0.00638

AC:

270

AN:

42316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

164

328

491

655

819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0319

AC:

4858

AN:

152302

Hom.:

278

Cov.:

AF XY:

0.0304

AC XY:

2267

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.111

AC:

4633

AN:

41554

American (AMR)

AF:

0.0106

AC:

162

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68032

Other (OTH)

AF:

0.0171

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

221

443

664

886

1107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0243

Hom.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.22

PhyloP100

0.52

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

Computational scores

Splicing

Publications

Other links and lift over