NM_198437.3:c.-6+1880A>C

Variant names:

• chr20-56390288-T-G
• rs6099128
• NM_198437.3:c.-6+1880A>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.-6+1880A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,398 control chromosomes in the GnomAD database, including 1,284 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 0.13 (1284 hom., cov: 31)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 6 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 (SAS) allele frequency at 95% confidence interval = 0.192 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.-6+1880A>C		intron	N/A	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.-377+268A>C		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.-377+268A>C		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.-6+1880A>C		intron	N/A	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.-6+268A>C		intron	N/A	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.-6+1655A>C		intron	N/A	ENSP00000216911.2	O14965

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19230 AN: 151288 Hom.: 1281 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.127 AC: 19247 AN: 151398 Hom.: 1284 Cov.: 31 AF XY: 0.129 AC XY: 9529 AN XY: 73932

African (AFR) AF: 0.157 AC: 6471 AN: 41160

American (AMR) AF: 0.104 AC: 1583 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3470

East Asian (EAS) AF: 0.124 AC: 639 AN: 5152

South Asian (SAS) AF: 0.203 AC: 973 AN: 4800

European-Finnish (FIN) AF: 0.147 AC: 1525 AN: 10374

Middle Eastern (MID) AF: 0.162 AC: 47 AN: 290

European-Non Finnish (NFE) AF: 0.105 AC: 7131 AN: 67920

Other (OTH) AF: 0.126 AC: 265 AN: 2098

Alfa AF: 0.111 Hom.: 1013

Bravo AF: 0.126

Asia WGS AF: 0.152 AC: 529 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	3.7
DANN	Benign	0.74
PhyloP100		-0.83
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: rs6099128; hg19: chr20-54965344;