20-56391393-A-G

Variant summary

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

The NM_198437.3(AURKA):c.-6+775T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 152,360 control chromosomes in the GnomAD database, including 72,204 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 0.97 (72204 hom., cov: 33)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AURKA	NM_198437.3	c.-6+775T>C		intron_variant		ENST00000395915.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AURKA	ENST00000395915.8	c.-6+775T>C		intron_variant		1	NM_198437.3	P1

Frequencies

GnomAD3 genomes AF: 0.973 AC: 148181 AN: 152242 Hom.: 72155 Cov.: 33

Gnomad AFR AF: 0.956

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.968

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.973 AC: 148288 AN: 152360 Hom.: 72204 Cov.: 33 AF XY: 0.972 AC XY: 72396 AN XY: 74502

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.968

Alfa AF: 0.990 Hom.: 11469

Bravo AF: 0.969

Asia WGS AF: 0.924 AC: 3213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.3
Dann	Benign	0.50

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: rs911162; hg19: chr20-54966449;