rs6099126

Positions:

• chr20-56388247-C-T

Variant summary

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

The ENST00000395915.8(AURKA):​c.-5-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,119,980 control chromosomes in the GnomAD database, including 7,166 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 0.32 (3405 hom., cov: 0)
  • Exomes 𝑓: 0.048 (3761 hom.)
• Consequence: AURKA ENST00000395915.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKA	NM_198437.3	c.-5-45G>A		intron_variant		ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.-5-45G>A		intron_variant		1	NM_198437.3	ENSP00000379251	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 20158 AN: 63820 Hom.: 3397 Cov.: 0

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.0913

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.0561 AC: 14067 AN: 250872 Hom.: 1568 AF XY: 0.0495 AC XY: 6716 AN XY: 135750

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.0228

Gnomad SAS exome AF: 0.0370

Gnomad FIN exome AF: 0.00518

Gnomad NFE exome AF: 0.0254

Gnomad OTH exome AF: 0.0569

GnomAD4 exome AF: 0.0481 AC: 50766 AN: 1056054 Hom.: 3761 Cov.: 25 AF XY: 0.0475 AC XY: 24616 AN XY: 518440

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.0723

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.0517

Gnomad4 SAS exome AF: 0.0702

Gnomad4 FIN exome AF: 0.00974

Gnomad4 NFE exome AF: 0.0280

Gnomad4 OTH exome AF: 0.0909

GnomAD4 genome AF: 0.316 AC: 20200 AN: 63926 Hom.: 3405 Cov.: 0 AF XY: 0.304 AC XY: 9486 AN XY: 31214

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0871

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0845

Gnomad4 OTH AF: 0.275

Alfa AF: 0.0567 Hom.: 889

Bravo AF: 0.149

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.85

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: rs6099126; hg19: chr20-54963303; COSMIC: COSV53858766; COSMIC: COSV53858766;