20-56390845-C-A

Variant names:

• chr20-56390845-C-A
• rs1468055
• NM_198437.3:c.-6+1323G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198437.3(AURKA):​c.-6+1323G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,174 control chromosomes in the GnomAD database, including 2,194 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 0.15 (2194 hom., cov: 33)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 3 publications found

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]

AURKA Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3	c.-6+1323G>T		intron_variant	Intron 1 of 8	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.-6+1323G>T		intron_variant	Intron 1 of 8	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22313 AN: 152056 Hom.: 2192 Cov.: 33

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.147 AC: 22309 AN: 152174 Hom.: 2194 Cov.: 33 AF XY: 0.142 AC XY: 10562 AN XY: 74390

African (AFR) AF: 0.0466 AC: 1935 AN: 41520

American (AMR) AF: 0.156 AC: 2382 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3466

East Asian (EAS) AF: 0.0216 AC: 112 AN: 5182

South Asian (SAS) AF: 0.157 AC: 759 AN: 4826

European-Finnish (FIN) AF: 0.0964 AC: 1020 AN: 10582

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14404 AN: 67990

Other (OTH) AF: 0.171 AC: 361 AN: 2112

Alfa AF: 0.196 Hom.: 7071

Bravo AF: 0.145

Asia WGS AF: 0.105 AC: 366 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	3.5
DANN	Benign	0.67
PhyloP100		0.072
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1468055; hg19: chr20-54965901;