rs6092309

Variant names:

• chr20-56386661-G-A
• rs6092309
• NM_198437.3:c.43-128C>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.43-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,075,078 control chromosomes in the GnomAD database, including 421 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 0.032 (278 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (143 hom.)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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.43-128C>T		intron	N/A	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.145-128C>T		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.145-128C>T		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.43-128C>T		intron	N/A	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.43-128C>T		intron	N/A	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.43-128C>T		intron	N/A	ENSP00000216911.2	O14965

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4845 AN: 152184 Hom.: 279 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.00342 AC: 3160 AN: 922776 Hom.: 143 AF XY: 0.00285 AC XY: 1349 AN XY: 472518

African (AFR) AF: 0.115 AC: 2520 AN: 21860

American (AMR) AF: 0.00672 AC: 224 AN: 33314

Ashkenazi Jewish (ASJ) AF: 0.0000488 AC: 1 AN: 20480

East Asian (EAS) AF: 0.00 AC: 0 AN: 34204

South Asian (SAS) AF: 0.000289 AC: 19 AN: 65854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36512

Middle Eastern (MID) AF: 0.00786 AC: 35 AN: 4454

European-Non Finnish (NFE) AF: 0.000137 AC: 91 AN: 663782

Other (OTH) AF: 0.00638 AC: 270 AN: 42316

GnomAD4 genome AF: 0.0319 AC: 4858 AN: 152302 Hom.: 278 Cov.: 33 AF XY: 0.0304 AC XY: 2267 AN XY: 74474

African (AFR) AF: 0.111 AC: 4633 AN: 41554

American (AMR) AF: 0.0106 AC: 162 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68032

Other (OTH) AF: 0.0171 AC: 36 AN: 2106

Alfa AF: 0.0243 Hom.: 57

Bravo AF: 0.0369

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.22
PhyloP100		0.52
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: rs6092309; hg19: chr20-54961717;