Genetic Variant BCO2:c.736+5A>C (chr11-112194760-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031938.7(BCO2):c.736+5A>C variant causes a splice region, 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_region, intron

Scores

Splicing: ADA: 0.00007611

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

15 publications found

Variant links:

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]

BCO2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BCO2	NM_031938.7 link	c.736+5A>C		splice_region_variant, intron_variant	Intron 5 of 11	ENST00000357685.11	NP_114144.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCO2	ENST00000357685.11 link	c.736+5A>C		splice_region_variant, intron_variant	Intron 5 of 11	1	NM_031938.7	ENSP00000350314.5

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57387

AN:

151818

Hom.:

11184

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.383

AC:

92849

AN:

242740

AF XY:

0.389

show subpopulations

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 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.:

AF XY:

0.360

AC XY:

252090

AN XY:

700874

show subpopulations

African (AFR)

AF:

0.466

AC:

14750

AN:

31644

American (AMR)

AF:

0.368

AC:

15529

AN:

42198

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

9309

AN:

25624

East Asian (EAS)

AF:

0.437

AC:

17088

AN:

39118

South Asian (SAS)

AF:

0.577

AC:

47984

AN:

83194

European-Finnish (FIN)

AF:

0.262

AC:

13991

AN:

53324

Middle Eastern (MID)

AF:

0.427

AC:

2417

AN:

5656

European-Non Finnish (NFE)

AF:

0.331

AC:

352250

AN:

1063464

Other (OTH)

AF:

0.371

AC:

21689

AN:

58436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14289

28578

42867

57156

71445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11444

22888

34332

45776

57220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.378

AC:

57453

AN:

151936

Hom.:

11211

Cov.:

AF XY:

0.379

AC XY:

28178

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.454

AC:

18811

AN:

41406

American (AMR)

AF:

0.369

AC:

5629

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1282

AN:

3472

East Asian (EAS)

AF:

0.473

AC:

2444

AN:

5164

South Asian (SAS)

AF:

0.596

AC:

2868

AN:

4810

European-Finnish (FIN)

AF:

0.258

AC:

2721

AN:

10562

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.332

AC:

22537

AN:

67942

Other (OTH)

AF:

0.387

AC:

819

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1789

3578

5368

7157

8946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.340

Hom.:

5878

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

(source)

DANN

Benign

0.59

PhyloP100

0.34

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over