NM_031938.7:c.418A>G

Variant names:

• chr11-112193598-A-G
• NM_031938.7:c.418A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031938.7(BCO2):​c.418A>G​(p.Ile140Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: BCO2 NM_031938.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.84
• 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]

ENSG00000255292 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

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.418A>G	p.Ile140Val	missense	Exon 3 of 12	NP_114144.5
	BCO2	NM_001037290.4		c.316A>G	p.Ile106Val	missense	Exon 3 of 12	NP_001032367.3	Q9BYV7-2
	BCO2	NM_001256397.3		c.316A>G	p.Ile106Val	missense	Exon 3 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.418A>G	p.Ile140Val	missense	Exon 3 of 12	ENSP00000350314.5	Q9BYV7-1
	BCO2	ENST00000438022.5	TSL:1	c.316A>G	p.Ile106Val	missense	Exon 3 of 12	ENSP00000414843.1	Q9BYV7-2
	BCO2	ENST00000531169.5	TSL:1	c.316A>G	p.Ile106Val	missense	Exon 3 of 13	ENSP00000437053.1	Q9BYV7-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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	0.23
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.91	N
REVEL	Pathogenic	0.74
Sift	Benign	0.067	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.74		Gain of sheet (P = 0.0827)
MVP		0.95
MPC		0.35
ClinPred		0.96	D
GERP RS		5.6
PromoterAI		-0.0043	Neutral
Varity_R		0.29
gMVP		0.67
Mutation Taster		=74/26	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

Other links and lift over

hg19: chr11-112064321;