11-112194731-A-C

Position:

• chr11-112194731-A-C

Variant summary

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

The NM_031938.7(BCO2):​c.712A>C​(p.Met238Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCO2 NM_031938.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38

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]

ACMG classification

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	c.712A>C	p.Met238Leu	missense_variant	5/12	ENST00000357685.11	NP_114144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCO2	ENST00000357685.11	c.712A>C	p.Met238Leu	missense_variant	5/12	1	NM_031938.7	ENSP00000350314	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2022

The c.712A>C (p.M238L) alteration is located in exon 5 (coding exon 5) of the BCO2 gene. This alteration results from a A to C substitution at nucleotide position 712, causing the methionine (M) at amino acid position 238 to be replaced by a leucine (L). 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	0.15
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Uncertain	0.52	D;.;.;.;.
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T;.;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	1.9	L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Pathogenic	0.65
Sift	Uncertain	0.013	D;D;D;D;D
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.94	P;.;.;.;.
Vest4		0.47
MutPred		0.71		Loss of disorder (P = 0.1473);.;.;.;.;
MVP		0.74
MPC		0.063
ClinPred		0.72	D
GERP RS		1.4
Varity_R		0.51
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-112065454;