rs732417

Positions:

• chr20-56392009-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001424420.1(AURKA):​c.-553C>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 NM_001424420.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKA	NM_198437.3	c.-6+159C>G		intron_variant		ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.-6+159C>G		intron_variant		1	NM_198437.3	ENSP00000379251.3

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.00123

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0698

Gnomad4 OTH AF: 0.0864

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.0
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs732417; hg19: chr20-54967065;