rs35361223

Variant names:

• chr11-112179334-C-G
• rs35361223
• NM_031938.7:c.145C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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
• Publications: 10 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: Benign. The variant received -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.

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.145C>G	p.Arg49Gly	missense	Exon 2 of 12	NP_114144.5
	BCO2	NM_001037290.4		c.43C>G	p.Arg15Gly	missense	Exon 2 of 12	NP_001032367.3
	BCO2	NM_001256397.3		c.43C>G	p.Arg15Gly	missense	Exon 2 of 12	NP_001243326.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO2	ENST00000357685.11	TSL:1 MANE Select	c.145C>G	p.Arg49Gly	missense	Exon 2 of 12	ENSP00000350314.5
	BCO2	ENST00000438022.5	TSL:1	c.43C>G	p.Arg15Gly	missense	Exon 2 of 12	ENSP00000414843.1
	BCO2	ENST00000531169.5	TSL:1	c.43C>G	p.Arg15Gly	missense	Exon 2 of 13	ENSP00000437053.1

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

GnomAD2 exomes AF: 0.0381 AC: 9586 AN: 251442 AF XY: 0.0390

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 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

African (AFR) AF: 0.00744 AC: 249 AN: 33480

American (AMR) AF: 0.0283 AC: 1265 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0304 AC: 794 AN: 26136

East Asian (EAS) AF: 0.000856 AC: 34 AN: 39700

South Asian (SAS) AF: 0.0292 AC: 2520 AN: 86254

European-Finnish (FIN) AF: 0.0501 AC: 2675 AN: 53418

Middle Eastern (MID) AF: 0.0130 AC: 75 AN: 5768

European-Non Finnish (NFE) AF: 0.0527 AC: 58635 AN: 1111964

Other (OTH) AF: 0.0407 AC: 2457 AN: 60394

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

African (AFR) AF: 0.00849 AC: 353 AN: 41556

American (AMR) AF: 0.0230 AC: 352 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4824

European-Finnish (FIN) AF: 0.0490 AC: 519 AN: 10592

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0509 AC: 3465 AN: 68024

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

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 v4.9

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
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.027
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.24
Sift	Benign	0.099	T
Sift4G	Benign	0.23	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
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs35361223; hg19: chr11-112050057; COSMIC: COSV108199100; COSMIC: COSV108199100;