chr20-56386017-A-G

Variant names:

• chr20-56386017-A-G
• rs6014711
• NM_198437.3:c.319+240T>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.319+240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,114 control chromosomes in the GnomAD database, including 54,059 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 0.84 (54059 hom., cov: 31)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.871 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.319+240T>C		intron	N/A	NP_940839.1
	AURKA	NM_001424418.1		c.421+240T>C		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.421+240T>C		intron	N/A	NP_001411348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.319+240T>C		intron	N/A	ENSP00000379251.3
	AURKA	ENST00000312783.10	TSL:1	c.319+240T>C		intron	N/A	ENSP00000321591.6
	AURKA	ENST00000347343.6	TSL:1	c.319+240T>C		intron	N/A	ENSP00000216911.2

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128095 AN: 151996 Hom.: 54003 Cov.: 31

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.843 AC: 128208 AN: 152114 Hom.: 54059 Cov.: 31 AF XY: 0.841 AC XY: 62546 AN XY: 74358

African (AFR) AF: 0.838 AC: 34757 AN: 41488

American (AMR) AF: 0.884 AC: 13503 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2993 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4562 AN: 5178

South Asian (SAS) AF: 0.853 AC: 4113 AN: 4822

European-Finnish (FIN) AF: 0.809 AC: 8546 AN: 10564

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56864 AN: 67992

Other (OTH) AF: 0.852 AC: 1801 AN: 2114

Alfa AF: 0.838 Hom.: 98470

Bravo AF: 0.848

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.51
PhyloP100		-0.60
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: rs6014711; hg19: chr20-54961073;