rs7501331

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.1136C>T(p.Ala379Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,611,860 control chromosomes in the GnomAD database, including 42,137 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3081 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39056 hom. )

Consequence

BCO1
NM_017429.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.13

Publications

67 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=0.0023401678).

BP6

Variant 16-81280891-C-T is Benign according to our data. Variant chr16-81280891-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017429.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO1	NM_017429.3	MANE Select	c.1136C>T	p.Ala379Val	missense	Exon 8 of 11	NP_059125.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCO1	ENST00000258168.7	TSL:1 MANE Select	c.1136C>T	p.Ala379Val	missense	Exon 8 of 11	ENSP00000258168.2
BCO1	ENST00000563804.5	TSL:2	n.*760C>T		non_coding_transcript_exon	Exon 7 of 10	ENSP00000457910.1
BCO1	ENST00000563804.5	TSL:2	n.*760C>T		3_prime_UTR	Exon 7 of 10	ENSP00000457910.1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27050

AN:

152002

Hom.:

3074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0449

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.183

GnomAD2 exomes

AF:

0.211

AC:

53074

AN:

251278

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.0441

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.226

AC:

329596

AN:

1459740

Hom.:

39056

Cov.:

AF XY:

0.225

AC XY:

163436

AN XY:

726252

show subpopulations

African (AFR)

AF:

0.0366

AC:

1225

AN:

33474

American (AMR)

AF:

0.171

AC:

7656

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3759

AN:

26112

East Asian (EAS)

AF:

0.148

AC:

5863

AN:

39698

South Asian (SAS)

AF:

0.195

AC:

16816

AN:

86192

European-Finnish (FIN)

AF:

0.322

AC:

17204

AN:

53388

Middle Eastern (MID)

AF:

0.161

AC:

930

AN:

5766

European-Non Finnish (NFE)

AF:

0.237

AC:

263430

AN:

1110080

Other (OTH)

AF:

0.211

AC:

12713

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

12245

24490

36734

48979

61224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8674

17348

26022

34696

43370

<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:

0.178

AC:

27070

AN:

152120

Hom.:

3081

Cov.:

AF XY:

0.181

AC XY:

13452

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0448

AC:

1859

AN:

41518

American (AMR)

AF:

0.186

AC:

2835

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

525

AN:

3472

East Asian (EAS)

AF:

0.167

AC:

866

AN:

5182

South Asian (SAS)

AF:

0.187

AC:

903

AN:

4822

European-Finnish (FIN)

AF:

0.320

AC:

3376

AN:

10566

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16149

AN:

67966

Other (OTH)

AF:

0.185

AC:

391

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1084

2168

3252

4336

5420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.199

Hom.:

6900

Bravo

AF:

0.163

TwinsUK

AF:

0.235

AC:

870

ALSPAC

AF:

0.234

AC:

901

ESP6500AA

AF:

0.0509

AC:

224

ESP6500EA

AF:

0.233

AC:

2007

ExAC

AF:

0.212

AC:

25720

Asia WGS

AF:

0.195

AC:

679

AN:

3478

EpiCase

AF:

0.227

EpiControl

AF:

0.226

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

2.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

REVEL

Benign

0.21

Sift

Benign

0.15

Sift4G

Benign

0.21

Polyphen

0.12

Vest4

0.035

MPC

0.11

ClinPred

0.019

GERP RS

4.6

Varity_R

0.16

gMVP

0.58

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over