rs2180691

Positions:

• chr20-56389305-G-A
• chr20-56389305-G-T

Variant summary

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

The NM_198437.3(AURKA):​c.-5-1103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,866 control chromosomes in the GnomAD database, including 17,931 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 0.44 (17931 hom., cov: 31)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AURKA	NM_198437.3	c.-5-1103C>T		intron_variant		ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.-5-1103C>T		intron_variant		1	NM_198437.3	ENSP00000379251	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66501 AN: 151746 Hom.: 17886 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.439 AC: 66598 AN: 151866 Hom.: 17931 Cov.: 31 AF XY: 0.439 AC XY: 32555 AN XY: 74220

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.400

Alfa AF: 0.303 Hom.: 11573

Bravo AF: 0.458

Asia WGS AF: 0.541 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.57

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: rs2180691; hg19: chr20-54964361;