Variant 13-72746504-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024808.5(BORA):c.875A>G(p.Gln292Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,605,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

BORA
NM_024808.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

BORA (HGNC:24724): (BORA aurora kinase A activator) BORA is an activator of the protein kinase Aurora A (AURKA; MIM 603072), which is required for centrosome maturation, spindle assembly, and asymmetric protein localization during mitosis (Hutterer et al., 2006 [PubMed 16890155]).[supplied by OMIM, Mar 2008]

BORA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07943994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BORA	NM_024808.5 linkuse as main transcript	c.875A>G	p.Gln292Arg	missense_variant	10/12	ENST00000390667.11	NP_079084.4
BORA	NM_001286746.3 linkuse as main transcript	c.875A>G	p.Gln292Arg	missense_variant	10/12		NP_001273675.2
BORA	NM_001366664.2 linkuse as main transcript	c.722A>G	p.Gln241Arg	missense_variant	8/10		NP_001353593.1
BORA	NM_001286747.2 linkuse as main transcript	c.665A>G	p.Gln222Arg	missense_variant	9/11		NP_001273676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORA	ENST00000390667.11 linkuse as main transcript	c.875A>G	p.Gln292Arg	missense_variant	10/12	1	NM_024808.5	ENSP00000375082	P1	Q6PGQ7-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000488

AC:

AN:

245658

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

133630

show subpopulations

Gnomad AFR exome

AF:

0.0000661

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000987

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1453146

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

721392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000371

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.0000828

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.875A>G (p.Q292R) alteration is located in exon 10 (coding exon 9) of the BORA gene. This alteration results from a A to G substitution at nucleotide position 875, causing the glutamine (Q) at amino acid position 292 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.016

T;T;.

Eigen

Benign

-0.0094

Eigen_PC

Benign

0.080

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.59

.;.;N

REVEL

Benign

0.027

Sift

Benign

0.39

.;.;T

Sift4G

Uncertain

0.054

T;T;T

Polyphen

0.87

P;.;.

Vest4

0.077

MVP

0.31

MPC

0.28

ClinPred

0.076

GERP RS

3.6

gMVP

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over