rs16979829

Variant names:

• chr20-56371994-T-G
• rs16979829
• NM_198437.3:c.855-1335A>C

Variant summary

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

The ENST00000395915.8(AURKA):​c.855-1335A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 152,310 control chromosomes in the GnomAD database, including 768 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 0.073 (768 hom., cov: 32)
• Consequence: AURKA ENST00000395915.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395915.8. 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.855-1335A>C		intron	N/A	NP_940839.1
	AURKA	NM_001424418.1		c.957-1335A>C		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.957-1335A>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.855-1335A>C		intron	N/A	ENSP00000379251.3
	AURKA	ENST00000312783.10	TSL:1	c.855-1335A>C		intron	N/A	ENSP00000321591.6
	AURKA	ENST00000347343.6	TSL:1	c.855-1335A>C		intron	N/A	ENSP00000216911.2

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11108 AN: 152190 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0730 AC: 11118 AN: 152310 Hom.: 768 Cov.: 32 AF XY: 0.0708 AC XY: 5273 AN XY: 74470

African (AFR) AF: 0.181 AC: 7507 AN: 41544

American (AMR) AF: 0.0367 AC: 561 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4828

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10620

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0343 AC: 2332 AN: 68030

Other (OTH) AF: 0.0676 AC: 143 AN: 2116

Alfa AF: 0.0439 Hom.: 683

Bravo AF: 0.0784

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.26
PhyloP100		0.23
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: rs16979829; hg19: chr20-54947050;