11-112179431-A-G

Variant summary

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

The NM_031938.7(BCO2):ā€‹c.242A>Gā€‹(p.Asn81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000021 ( 1 hom. )

Consequence

BCO2
NM_031938.7 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.953
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]

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=0.23878166).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BCO2NM_031938.7 linkc.242A>G p.Asn81Ser missense_variant 2/12 ENST00000357685.11 NP_114144.5 Q9BYV7-1B2RCV8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BCO2ENST00000357685.11 linkc.242A>G p.Asn81Ser missense_variant 2/121 NM_031938.7 ENSP00000350314.5 Q9BYV7-1
ENSG00000255292ENST00000532699.1 linkn.*55+8757A>G intron_variant 3 ENSP00000456434.1 H3BRW5

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251486
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
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:
0.00000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461894
Hom.:
1
Cov.:
31
AF XY:
0.0000248
AC XY:
18
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.0000151

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 submitterclinical testingAmbry GeneticsDec 06, 2024The c.242A>G (p.N81S) alteration is located in exon 2 (coding exon 2) of the BCO2 gene. This alteration results from a A to G substitution at nucleotide position 242, causing the asparagine (N) at amino acid position 81 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
0.062
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
12
DANN
Benign
0.67
DEOGEN2
Uncertain
0.46
T;.;.;.;.
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.74
T;D;.;T;T
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.24
T;T;T;T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
1.3
L;L;.;.;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.5
N;N;N;N;N
REVEL
Benign
0.22
Sift
Benign
0.68
T;T;T;T;T
Sift4G
Benign
0.87
T;T;T;T;T
Polyphen
0.0030
B;.;.;.;.
Vest4
0.13
MutPred
0.40
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;.;
MVP
0.59
MPC
0.055
ClinPred
0.017
T
GERP RS
-2.3
Varity_R
0.065
gMVP
0.47

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.

Other links and lift over

dbSNP: rs1362305032; hg19: chr11-112050154; API