Variant 11-112199792-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031938.7(BCO2):c.830C>G(p.Thr277Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

BCO2
NM_031938.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.574

Variant links:

Genes affected

BCO2 (HGNC:18503): (beta-carotene oxygenase 2) This gene encodes an enzyme which oxidizes carotenoids such as beta-carotene during the biosynthesis of vitamin A. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

BCO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCO2	NM_031938.7 linkuse as main transcript	c.830C>G	p.Thr277Arg	missense_variant	6/12	ENST00000357685.11	NP_114144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCO2	ENST00000357685.11 linkuse as main transcript	c.830C>G	p.Thr277Arg	missense_variant	6/12	1	NM_031938.7	ENSP00000350314	P2	Q9BYV7-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000410

AC:

103

AN:

251422

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00814

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000235

AC:

344

AN:

1461708

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

155

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00685

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000289

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000938

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

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 31, 2023

The c.830C>G (p.T277R) alteration is located in exon 6 (coding exon 6) of the BCO2 gene. This alteration results from a C to G substitution at nucleotide position 830, causing the threonine (T) at amino acid position 277 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

0.077

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.29

CADD

Benign

8.3

DANN

Benign

0.73

DEOGEN2

Benign

0.33

T;.;.;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.76

T;T;.;T;T;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.0087

T;T;T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

-0.33

N;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.31

N;N;N;N;N;N

REVEL

Uncertain

0.36

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.98

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.12

MVP

0.40

MPC

0.068

ClinPred

0.013

GERP RS

-1.5

Varity_R

0.054

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.27

Position offset: 35

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