rs732417

Variant names:

• chr20-56392009-G-C
• rs732417
• ENST00000347343.6:c.-72C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000347343.6(AURKA):​c.-72C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 148,350 control chromosomes in the GnomAD database, including 671 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 0.087 (667 hom., cov: 31)
  • Exomes 𝑓: 0.14 (4 hom.)
• Consequence: AURKA ENST00000347343.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 12 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000347343.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.-6+159C>G		intron	N/A	NP_940839.1
	AURKA	NM_001424420.1		c.-553C>G		5_prime_UTR	Exon 1 of 11	NP_001411349.1
	AURKA	NM_001323303.2		c.-182C>G		5_prime_UTR	Exon 1 of 10	NP_001310232.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000347343.6	TSL:1	c.-72C>G		5_prime_UTR	Exon 1 of 9	ENSP00000216911.2
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.-6+159C>G		intron	N/A	ENSP00000379251.3
	AURKA	ENST00000312783.10	TSL:1	c.-116+159C>G		intron	N/A	ENSP00000321591.6

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 12884 AN: 148132 Hom.: 666 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.00144

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0874

GnomAD4 exome AF: 0.141 AC: 13 AN: 92 Hom.: 4 Cov.: 0 AF XY: 0.143 AC XY: 12 AN XY: 84

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 1.00 AC: 6 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0429 AC: 3 AN: 70

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.0870 AC: 12903 AN: 148258 Hom.: 667 Cov.: 31 AF XY: 0.0845 AC XY: 6088 AN XY: 72012

African (AFR) AF: 0.141 AC: 5686 AN: 40430

American (AMR) AF: 0.102 AC: 1455 AN: 14288

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 241 AN: 3454

East Asian (EAS) AF: 0.00123 AC: 6 AN: 4860

South Asian (SAS) AF: 0.0459 AC: 213 AN: 4636

European-Finnish (FIN) AF: 0.0367 AC: 360 AN: 9798

Middle Eastern (MID) AF: 0.121 AC: 34 AN: 282

European-Non Finnish (NFE) AF: 0.0698 AC: 4715 AN: 67552

Other (OTH) AF: 0.0864 AC: 177 AN: 2048

Alfa AF: 0.0731 Hom.: 56

Bravo AF: 0.0922

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.0
DANN	Benign	0.57
PhyloP100		0.064
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs732417; hg19: chr20-54967065;