Variant 13-72743540-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024808.5(BORA):c.392C>G(p.Thr131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,454,668 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: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

BORA
NM_024808.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042731166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BORA	NM_024808.5 linkuse as main transcript	c.392C>G	p.Thr131Ser	missense_variant	6/12	ENST00000390667.11	NP_079084.4
BORA	NM_001286746.3 linkuse as main transcript	c.392C>G	p.Thr131Ser	missense_variant	6/12		NP_001273675.2
BORA	NM_001366664.2 linkuse as main transcript	c.239C>G	p.Thr80Ser	missense_variant	4/10		NP_001353593.1
BORA	NM_001286747.2 linkuse as main transcript	c.182C>G	p.Thr61Ser	missense_variant	5/11		NP_001273676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORA	ENST00000390667.11 linkuse as main transcript	c.392C>G	p.Thr131Ser	missense_variant	6/12	1	NM_024808.5	ENSP00000375082	P1	Q6PGQ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

246088

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000671

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1454668

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000703

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

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

May 01, 2024

The c.392C>G (p.T131S) alteration is located in exon 6 (coding exon 5) of the BORA gene. This alteration results from a C to G substitution at nucleotide position 392, causing the threonine (T) at amino acid position 131 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.6

DANN

Benign

0.27

DEOGEN2

Benign

0.0065

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.060

.;.;N

REVEL

Benign

0.020

Sift

Benign

0.83

.;.;T

Sift4G

Benign

0.86

T;T;T

Polyphen

0.044

B;.;.

Vest4

0.13

MVP

0.25

MPC

0.22

ClinPred

0.042

GERP RS

3.3

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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