20-56370155-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198437.3(AURKA):c.*3A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 1,612,342 control chromosomes in the GnomAD database, including 484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (39 hom., cov: 32)
  • Exomes 𝑓: 0.022 (445 hom.)
• Consequence: AURKA NM_198437.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 20-56370155-T-G is Benign according to our data. Variant chr20-56370155-T-G is described in ClinVar as [Benign]. Clinvar id is 3037417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2485/152334) while in subpopulation NFE AF= 0.0214 (1454/68034). AF 95% confidence interval is 0.0205. There are 39 homozygotes in gnomad4. There are 1337 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2485 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AURKA	NM_198437.3	c.*3A>C		3_prime_UTR_variant	9/9	ENST00000395915.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AURKA	ENST00000395915.8	c.*3A>C		3_prime_UTR_variant	9/9	1	NM_198437.3	P1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2485 AN: 152216 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.0187 AC: 4694 AN: 251408 Hom.: 73 AF XY: 0.0193 AC XY: 2625 AN XY: 135876

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.00838

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0136

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0230

Gnomad OTH exome AF: 0.0182

GnomAD4 exome AF: 0.0216 AC: 31489 AN: 1460008 Hom.: 445 Cov.: 32 AF XY: 0.0213 AC XY: 15503 AN XY: 726308

Gnomad4 AFR exome AF: 0.00287

Gnomad4 AMR exome AF: 0.00847

Gnomad4 ASJ exome AF: 0.00390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.0498

Gnomad4 NFE exome AF: 0.0232

Gnomad4 OTH exome AF: 0.0203

GnomAD4 genome AF: 0.0163 AC: 2485 AN: 152334 Hom.: 39 Cov.: 32 AF XY: 0.0179 AC XY: 1337 AN XY: 74490

Gnomad4 AFR AF: 0.00430

Gnomad4 AMR AF: 0.00849

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0174 Hom.: 13

Bravo AF: 0.0120

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.0206

EpiControl AF: 0.0213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

AURKA-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	2.7
Dann	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs34361943; hg19: chr20-54945211; COSMIC: COSV57167435; COSMIC: COSV57167435;