rs7123686

Positions:

• chr11-112194760-A-C
• chr11-112194760-A-T

Variant summary

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

The NM_031938.7(BCO2):​c.736+5A>C variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,554,594 control chromosomes in the GnomAD database, including 102,159 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11211 hom., cov: 31)
  • Exomes 𝑓: 0.35 (90948 hom.)
• Consequence: BCO2 NM_031938.7 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 0.00007611
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCO2	NM_031938.7	c.736+5A>C		splice_donor_5th_base_variant, intron_variant		ENST00000357685.11	NP_114144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCO2	ENST00000357685.11	c.736+5A>C		splice_donor_5th_base_variant, intron_variant		1	NM_031938.7	ENSP00000350314	P2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57387 AN: 151818 Hom.: 11184 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.383 AC: 92849 AN: 242740 Hom.: 18908 AF XY: 0.389 AC XY: 51132 AN XY: 131380

Gnomad AFR exome AF: 0.453

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.479

Gnomad SAS exome AF: 0.582

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.353 AC: 495007 AN: 1402658 Hom.: 90948 Cov.: 23 AF XY: 0.360 AC XY: 252090 AN XY: 700874

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.577

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.378 AC: 57453 AN: 151936 Hom.: 11211 Cov.: 31 AF XY: 0.379 AC XY: 28178 AN XY: 74256

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.387

Alfa AF: 0.336 Hom.: 5066

Bravo AF: 0.385

Asia WGS AF: 0.553 AC: 1923 AN: 3478

EpiCase AF: 0.342

EpiControl AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.080		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: rs7123686; hg19: chr11-112065483;