rs8173

Positions:

• chr20-56369735-C-G
• chr20-56369735-C-T

Variant summary

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

The NM_198437.3(AURKA):​c.*423G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 362,708 control chromosomes in the GnomAD database, including 30,747 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 0.42 (15924 hom., cov: 33)
  • Exomes 𝑓: 0.35 (14823 hom.)
• Consequence: AURKA NM_198437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKA	NM_198437.3	c.*423G>C		3_prime_UTR_variant	9/9	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.*423G>C		3_prime_UTR_variant	9/9	1	NM_198437.3	ENSP00000379251	P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64163 AN: 151944 Hom.: 15872 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.346 AC: 72806 AN: 210644 Hom.: 14823 Cov.: 0 AF XY: 0.345 AC XY: 36322 AN XY: 105184

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.423 AC: 64272 AN: 152064 Hom.: 15924 Cov.: 33 AF XY: 0.428 AC XY: 31771 AN XY: 74316

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.388

Alfa AF: 0.168 Hom.: 295

Bravo AF: 0.437

Asia WGS AF: 0.521 AC: 1813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.60

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: rs8173; hg19: chr20-54944791;