20-56388247-C-T

Variant names:

• chr20-56388247-C-T
• rs6099126
• NM_198437.3:c.-5-45G>A

Variant summary

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

The NM_198437.3(AURKA):​c.-5-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,119,980 control chromosomes in the GnomAD database, including 7,166 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 0.32 (3405 hom., cov: 0)
  • Exomes 𝑓: 0.048 (3761 hom.)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKA	NM_198437.3	c.-5-45G>A		intron_variant	Intron 1 of 8	ENST00000395915.8	NP_940839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKA	ENST00000395915.8	c.-5-45G>A		intron_variant	Intron 1 of 8	1	NM_198437.3	ENSP00000379251.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 20158 AN: 63820 Hom.: 3397 Cov.: 0

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.0913

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.0561 AC: 14067 AN: 250872 AF XY: 0.0495

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.0228

Gnomad FIN exome AF: 0.00518

Gnomad NFE exome AF: 0.0254

Gnomad OTH exome AF: 0.0569

GnomAD4 exome AF: 0.0481 AC: 50766 AN: 1056054 Hom.: 3761 Cov.: 25 AF XY: 0.0475 AC XY: 24616 AN XY: 518440

African (AFR) AF: 0.468 AC: 13620 AN: 29074

American (AMR) AF: 0.0723 AC: 2096 AN: 28982

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 2853 AN: 16350

East Asian (EAS) AF: 0.0517 AC: 675 AN: 13050

South Asian (SAS) AF: 0.0702 AC: 3300 AN: 47004

European-Finnish (FIN) AF: 0.00974 AC: 270 AN: 27724

Middle Eastern (MID) AF: 0.142 AC: 620 AN: 4378

European-Non Finnish (NFE) AF: 0.0280 AC: 23787 AN: 850474

Other (OTH) AF: 0.0909 AC: 3545 AN: 39018

GnomAD4 genome AF: 0.316 AC: 20200 AN: 63926 Hom.: 3405 Cov.: 0 AF XY: 0.304 AC XY: 9486 AN XY: 31214

African (AFR) AF: 0.529 AC: 16441 AN: 31088

American (AMR) AF: 0.222 AC: 1037 AN: 4678

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 373 AN: 1394

East Asian (EAS) AF: 0.0871 AC: 118 AN: 1354

South Asian (SAS) AF: 0.133 AC: 192 AN: 1440

European-Finnish (FIN) AF: 0.0213 AC: 60 AN: 2818

Middle Eastern (MID) AF: 0.320 AC: 39 AN: 122

European-Non Finnish (NFE) AF: 0.0845 AC: 1687 AN: 19974

Other (OTH) AF: 0.275 AC: 234 AN: 850

Alfa AF: 0.0556 Hom.: 2208

Bravo AF: 0.149

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		-0.19
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: rs6099126; hg19: chr20-54963303; COSMIC: COSV53858766; COSMIC: COSV53858766;