11-112194731-A-C

Variant names:

• chr11-112194731-A-C
• rs765749418
• NM_031938.7:c.712A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031938.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO2	NM_031938.7	MANE Select	c.712A>C	p.Met238Leu	missense	Exon 5 of 12	NP_114144.5
	BCO2	NM_001037290.4		c.610A>C	p.Met204Leu	missense	Exon 5 of 12	NP_001032367.3	Q9BYV7-2
	BCO2	NM_001256397.3		c.610A>C	p.Met204Leu	missense	Exon 5 of 12	NP_001243326.2	Q9BYV7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO2	ENST00000357685.11	TSL:1 MANE Select	c.712A>C	p.Met238Leu	missense	Exon 5 of 12	ENSP00000350314.5	Q9BYV7-1
	BCO2	ENST00000438022.5	TSL:1	c.610A>C	p.Met204Leu	missense	Exon 5 of 12	ENSP00000414843.1	Q9BYV7-2
	BCO2	ENST00000531169.5	TSL:1	c.610A>C	p.Met204Leu	missense	Exon 5 of 13	ENSP00000437053.1	Q9BYV7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
PhyloP100		5.4
Varity_R		0.51
gMVP		0.67
Mutation Taster		=63/37	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs765749418; hg19: chr11-112065454;