17-8207608-C-G

Variant names:

• chr17-8207608-C-G
• rs372199124
• NM_004217.4:c.169G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001313954.2(AURKB):​c.-298G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: AURKB NM_001313954.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.620
• Publications: 1 publications found

Genes affected

AURKB (HGNC:11390): (aurora kinase B) This gene encodes a member of the aurora kinase subfamily of serine/threonine kinases. The genes encoding the other two members of this subfamily are located on chromosomes 19 and 20. These kinases participate in the regulation of alignment and segregation of chromosomes during mitosis and meiosis through association with microtubules. A pseudogene of this gene is located on chromosome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04264745).
• BS2: High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001313954.2. 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
	AURKB	NM_004217.4	MANE Select	c.169G>C	p.Val57Leu	missense	Exon 4 of 9	NP_004208.2	Q96GD4-1
	AURKB	NM_001313954.2		c.-298G>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 9	NP_001300883.1
	AURKB	NM_001313955.2		c.-55G>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001300884.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKB	ENST00000585124.6	TSL:1 MANE Select	c.169G>C	p.Val57Leu	missense	Exon 4 of 9	ENSP00000463999.1	Q96GD4-1
	AURKB	ENST00000316199.10	TSL:1	c.169G>C	p.Val57Leu	missense	Exon 4 of 9	ENSP00000313950.6	Q96GD4-5
	AURKB	ENST00000578549.5	TSL:1	c.169G>C	p.Val57Leu	missense	Exon 3 of 8	ENSP00000462207.1	Q96GD4-2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152176 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000716 AC: 18 AN: 251380 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000147 AC: 215 AN: 1461698 Hom.: 0 Cov.: 32 AF XY: 0.000140 AC XY: 102 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000183 AC: 203 AN: 1111852

Other (OTH) AF: 0.000199 AC: 12 AN: 60394

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152176 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.62
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.019
Sift	Benign	0.75	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.16		Loss of methylation at K56 (P = 0.0341)
MVP		0.80
MPC		0.19
ClinPred		0.023	T
GERP RS		1.8
PromoterAI		0.0023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.24
Mutation Taster		=91/9	polymorphism

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: rs372199124; hg19: chr17-8110926; COSMIC: COSV60246780;