rs12420140

Positions:

• chr11-112200571-G-A

Variant summary

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

The NM_031938.7(BCO2):​c.866-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,560,866 control chromosomes in the GnomAD database, including 52,254 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3600 hom., cov: 32)
  • Exomes 𝑓: 0.25 (48654 hom.)
• Consequence: BCO2 NM_031938.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCO2	NM_031938.7	c.866-42G>A		intron_variant		ENST00000357685.11	NP_114144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCO2	ENST00000357685.11	c.866-42G>A		intron_variant		1	NM_031938.7	ENSP00000350314.5

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28708 AN: 151996 Hom.: 3597 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.206 AC: 46510 AN: 225996 Hom.: 6009 AF XY: 0.204 AC XY: 25182 AN XY: 123226

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.00221

Gnomad SAS exome AF: 0.0941

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.251 AC: 353865 AN: 1408752 Hom.: 48654 Cov.: 26 AF XY: 0.246 AC XY: 172599 AN XY: 700778

Gnomad4 AFR exome AF: 0.0376

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.00507

Gnomad4 SAS exome AF: 0.0982

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.189 AC: 28714 AN: 152114 Hom.: 3600 Cov.: 32 AF XY: 0.185 AC XY: 13778 AN XY: 74340

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.0940

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.172

Alfa AF: 0.237 Hom.: 2701

Bravo AF: 0.183

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.2
DANN	Benign	0.77

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: rs12420140; hg19: chr11-112071294; COSMIC: COSV63063187;