rs35361223

Positions:

• chr11-112179334-C-G
• chr11-112179334-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031938.7(BCO2):​c.145C>G​(p.Arg49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,614,098 control chromosomes in the GnomAD database, including 1,902 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.033 (117 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1785 hom.)
• Consequence: BCO2 NM_031938.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029857457).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCO2	NM_031938.7	c.145C>G	p.Arg49Gly	missense_variant	2/12	ENST00000357685.11	NP_114144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCO2	ENST00000357685.11	c.145C>G	p.Arg49Gly	missense_variant	2/12	1	NM_031938.7	ENSP00000350314.5
ENSG00000255292	ENST00000532699.1	n.*55+8660C>G		intron_variant		3		ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5017 AN: 152142 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00852

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.0381 AC: 9586 AN: 251442 Hom.: 243 AF XY: 0.0390 AC XY: 5298 AN XY: 135906

Gnomad AFR exome AF: 0.00849

Gnomad AMR exome AF: 0.0295

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0285

Gnomad FIN exome AF: 0.0473

Gnomad NFE exome AF: 0.0526

Gnomad OTH exome AF: 0.0415

GnomAD4 exome AF: 0.0470 AC: 68704 AN: 1461838 Hom.: 1785 Cov.: 31 AF XY: 0.0463 AC XY: 33702 AN XY: 727222

Gnomad4 AFR exome AF: 0.00744

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.0304

Gnomad4 EAS exome AF: 0.000856

Gnomad4 SAS exome AF: 0.0292

Gnomad4 FIN exome AF: 0.0501

Gnomad4 NFE exome AF: 0.0527

Gnomad4 OTH exome AF: 0.0407

GnomAD4 genome AF: 0.0330 AC: 5019 AN: 152260 Hom.: 117 Cov.: 32 AF XY: 0.0320 AC XY: 2383 AN XY: 74442

Gnomad4 AFR AF: 0.00849

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0490

Gnomad4 NFE AF: 0.0509

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0241 Hom.: 17

Bravo AF: 0.0299

TwinsUK AF: 0.0518 AC: 192

ALSPAC AF: 0.0488 AC: 188

ESP6500AA AF: 0.00863 AC: 38

ESP6500EA AF: 0.0495 AC: 425

ExAC AF: 0.0401 AC: 4869

Asia WGS AF: 0.0120 AC: 44 AN: 3478

EpiCase AF: 0.0463

EpiControl AF: 0.0443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	8.9
DANN	Benign	0.91
DEOGEN2	Benign	0.13	T;.;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.61	T;T;.;T;T
MetaRNN	Benign	0.0030	T;T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.34	N;N;.;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.099	T;T;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.045	B;.;.;.;.
Vest4		0.13
MPC		0.085
ClinPred		0.0061	T
GERP RS		0.32
Varity_R		0.15
gMVP		0.56

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

Other links and lift over

dbSNP: rs35361223; hg19: chr11-112050057;