16-81268089-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017429.3(BCO1):c.801A>T(p.Arg267Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,611,260 control chromosomes in the GnomAD database, including 139,175 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R267K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.34 ( 10103 hom., cov: 30)

Exomes 𝑓: 0.41 ( 129072 hom. )

Consequence

BCO1
NM_017429.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.33

Publications

70 publications found

Variant links:

Genes affected

BCO1 (HGNC:13815): (beta-carotene oxygenase 1) Vitamin A metabolism is important for vital processes such as vision, embryonic development, cell differentiation, and membrane and skin protection. The protein encoded by this gene is a key enzyme in beta-carotene metabolism to vitamin A. It catalyzes the oxidative cleavage of beta,beta-carotene into two retinal molecules. [provided by RefSeq, Jul 2008]

BCO1 Gene-Disease associations (from GenCC):

hereditary hypercarotenemia and vitamin A deficiency
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

BCO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8055906E-4).

BP6

Variant 16-81268089-A-T is Benign according to our data. Variant chr16-81268089-A-T is described in ClinVar as Benign. ClinVar VariationId is 1293223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3 link	c.801A>T	p.Arg267Ser	missense_variant	Exon 6 of 11	ENST00000258168.7	NP_059125.2	Q9HAY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCO1	ENST00000258168.7 link	c.801A>T	p.Arg267Ser	missense_variant	Exon 6 of 11	1	NM_017429.3	ENSP00000258168.2	Q9HAY6
BCO1	ENST00000563804.5 link	n.*425A>T		non_coding_transcript_exon_variant	Exon 5 of 10	2		ENSP00000457910.1	H3BV18
BCO1	ENST00000563804.5 link	n.*425A>T		3_prime_UTR_variant	Exon 5 of 10	2		ENSP00000457910.1	H3BV18

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51320

AN:

151442

Hom.:

10100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.367

GnomAD2 exomes

AF:

0.358

AC:

89612

AN:

250002

AF XY:

0.363

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.408

GnomAD4 exome

AF:

0.411

AC:

600556

AN:

1459698

Hom.:

129072

Cov.:

AF XY:

0.408

AC XY:

296560

AN XY:

726196

show subpopulations

African (AFR)

AF:

0.140

AC:

4698

AN:

33480

American (AMR)

AF:

0.303

AC:

13570

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

12055

AN:

26136

East Asian (EAS)

AF:

0.142

AC:

5624

AN:

39700

South Asian (SAS)

AF:

0.276

AC:

23786

AN:

86256

European-Finnish (FIN)

AF:

0.401

AC:

20603

AN:

51340

Middle Eastern (MID)

AF:

0.410

AC:

2363

AN:

5768

European-Non Finnish (NFE)

AF:

0.445

AC:

494417

AN:

1111920

Other (OTH)

AF:

0.388

AC:

23440

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20824

41647

62471

83294

104118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14508

29016

43524

58032

72540

<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:

0.339

AC:

51319

AN:

151562

Hom.:

10103

Cov.:

AF XY:

0.334

AC XY:

24719

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.151

AC:

6250

AN:

41296

American (AMR)

AF:

0.345

AC:

5250

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1626

AN:

3468

East Asian (EAS)

AF:

0.138

AC:

706

AN:

5116

South Asian (SAS)

AF:

0.266

AC:

1274

AN:

4782

European-Finnish (FIN)

AF:

0.390

AC:

4093

AN:

10490

Middle Eastern (MID)

AF:

0.490

AC:

143

AN:

292

European-Non Finnish (NFE)

AF:

0.454

AC:

30807

AN:

67882

Other (OTH)

AF:

0.364

AC:

766

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1596

3192

4789

6385

7981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.419

Hom.:

9077

Bravo

AF:

0.325

TwinsUK

AF:

0.447

AC:

1657

ALSPAC

AF:

0.437

AC:

1683

ESP6500AA

AF:

0.163

AC:

718

ESP6500EA

AF:

0.450

AC:

3866

ExAC

AF:

0.357

AC:

43352

Asia WGS

AF:

0.176

AC:

613

AN:

3478

EpiCase

AF:

0.456

EpiControl

AF:

0.449

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19103647) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.48

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.83

MetaRNN

Benign

0.00028

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.14

PhyloP100

-2.3

PrimateAI

Benign

0.39

PROVEAN

Benign

1.3

REVEL

Benign

0.28

Sift

Uncertain

0.0050

Sift4G

Benign

0.063

Polyphen

0.0020

Vest4

0.051

MutPred

0.20

Loss of MoRF binding (P = 0.0278);

MPC

0.060

ClinPred

0.030

GERP RS

-7.5

Varity_R

0.20

gMVP

0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over