20-56391393-A-G

Variant names:

• chr20-56391393-A-G
• rs911162
• NM_198437.3:c.-6+775T>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+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
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.-6+775T>C		intron	N/A	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.-486-728T>C		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.-486-728T>C		intron	N/A	NP_001411348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.-6+775T>C		intron	N/A	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.-115-728T>C		intron	N/A	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.-6+550T>C		intron	N/A	ENSP00000216911.2	O14965

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

African (AFR) AF: 0.956 AC: 39739 AN: 41572

American (AMR) AF: 0.961 AC: 14716 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3377 AN: 3472

East Asian (EAS) AF: 0.915 AC: 4744 AN: 5186

South Asian (SAS) AF: 0.916 AC: 4425 AN: 4830

European-Finnish (FIN) AF: 0.994 AC: 10560 AN: 10624

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67483 AN: 68044

Other (OTH) AF: 0.968 AC: 2048 AN: 2116

Alfa AF: 0.988 Hom.: 26370

Bravo AF: 0.969

Asia WGS AF: 0.924 AC: 3213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.67
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: rs911162; hg19: chr20-54966449;