rs6024840

Positions:

• chr20-56381651-A-G
• chr20-56381651-A-T

Variant summary

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

The NM_198437.3(AURKA):​c.567-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,564,156 control chromosomes in the GnomAD database, including 70,963 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 0.35 (10549 hom., cov: 32)
  • Exomes 𝑓: 0.28 (60414 hom.)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKA	NM_198437.3	c.567-80T>C		intron_variant		ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.567-80T>C		intron_variant		1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53174 AN: 151944 Hom.: 10517 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.278 AC: 392348 AN: 1412094 Hom.: 60414 AF XY: 0.279 AC XY: 196723 AN XY: 705078

Gnomad4 AFR exome AF: 0.506

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.350 AC: 53258 AN: 152062 Hom.: 10549 Cov.: 32 AF XY: 0.354 AC XY: 26294 AN XY: 74344

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.333

Alfa AF: 0.219 Hom.: 964

Bravo AF: 0.361

Asia WGS AF: 0.524 AC: 1823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.041
DANN	Benign	0.72

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: rs6024840; hg19: chr20-54956707; COSMIC: COSV57170165; COSMIC: COSV57170165;