20-56390932-C-G

Variant names:

• chr20-56390932-C-G
• rs1468056
• NM_198437.3:c.-6+1236G>C

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+1236G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,052 control chromosomes in the GnomAD database, including 30,033 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 0.60 (30033 hom., cov: 32)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3	c.-6+1236G>C		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+1236G>C		intron_variant	Intron 1 of 8	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91955 AN: 151934 Hom.: 30043 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.605 AC: 91961 AN: 152052 Hom.: 30033 Cov.: 32 AF XY: 0.616 AC XY: 45767 AN XY: 74302

African (AFR) AF: 0.355 AC: 14695 AN: 41450

American (AMR) AF: 0.639 AC: 9752 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4575 AN: 5162

South Asian (SAS) AF: 0.682 AC: 3286 AN: 4820

European-Finnish (FIN) AF: 0.856 AC: 9054 AN: 10580

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46509 AN: 67990

Other (OTH) AF: 0.603 AC: 1272 AN: 2110

Alfa AF: 0.657 Hom.: 4248

Bravo AF: 0.579

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.6
DANN	Benign	0.71
PhyloP100		-0.20
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: rs1468056; hg19: chr20-54965988;