chr20-56371124-T-C

Variant names:

• chr20-56371124-T-C
• rs16979826
• NM_198437.3:c.855-465A>G

Variant summary

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

The NM_198437.3(AURKA):​c.855-465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 151,920 control chromosomes in the GnomAD database, including 258 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 (258 hom., cov: 32)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 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.855-465A>G		intron	N/A	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.957-465A>G		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.957-465A>G		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.855-465A>G		intron	N/A	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.855-465A>G		intron	N/A	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.855-465A>G		intron	N/A	ENSP00000216911.2	O14965

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4871 AN: 151802 Hom.: 258 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0321 AC: 4878 AN: 151920 Hom.: 258 Cov.: 32 AF XY: 0.0314 AC XY: 2330 AN XY: 74240

African (AFR) AF: 0.110 AC: 4538 AN: 41396

American (AMR) AF: 0.0150 AC: 229 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 67960

Other (OTH) AF: 0.0280 AC: 59 AN: 2104

Alfa AF: 0.0406 Hom.: 119

Bravo AF: 0.0370

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		-0.11
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: rs16979826; hg19: chr20-54946180;