11-112193560-A-G

Variant names:

• chr11-112193560-A-G
• NM_031938.7:c.380A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031938.7(BCO2):​c.380A>G​(p.Gln127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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: 2.06

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

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=0.25748613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO2	NM_031938.7	c.380A>G	p.Gln127Arg	missense_variant	Exon 3 of 12	ENST00000357685.11	NP_114144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCO2	ENST00000357685.11	c.380A>G	p.Gln127Arg	missense_variant	Exon 3 of 12	1	NM_031938.7	ENSP00000350314.5
ENSG00000255292	ENST00000532699.1	n.*142A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000456434.1
ENSG00000255292	ENST00000532699.1	n.*142A>G		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000456434.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.380A>G (p.Q127R) alteration is located in exon 3 (coding exon 3) of the BCO2 gene. This alteration results from a A to G substitution at nucleotide position 380, causing the glutamine (Q) at amino acid position 127 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	0.076
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.34	T;.;.;.;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T;D;.;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.78	N;N;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.34	N;N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.016	B;.;.;.;.;.
Vest4		0.34
MutPred		0.45		Gain of MoRF binding (P = 0.0101);Gain of MoRF binding (P = 0.0101);.;.;.;.;
MVP		0.63
MPC		0.29
ClinPred		0.27	T
GERP RS		4.5
Varity_R		0.13
gMVP		0.71

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: chr11-112064283;