rs141781255

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_017429.3(BCO1):c.1622G>A(p.Cys541Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,613,678 control chromosomes in the GnomAD database, including 63 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 57 hom. )

Consequence

BCO1
NM_017429.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.928

Publications

9 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053551495).

BP6

Variant 16-81290555-G-A is Benign according to our data. Variant chr16-81290555-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 377022.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00657 (9601/1461428) while in subpopulation SAS AF = 0.0158 (1366/86258). AF 95% confidence interval is 0.0151. There are 57 homozygotes in GnomAdExome4. There are 5034 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 950 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3 link	c.1622G>A	p.Cys541Tyr	missense_variant	Exon 11 of 11	ENST00000258168.7	NP_059125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
BCO1	ENST00000258168.7 link	c.1622G>A	p.Cys541Tyr	missense_variant	Exon 11 of 11	1	NM_017429.3	ENSP00000258168.2
BCO1	ENST00000563804.5 link	n.*1246G>A		non_coding_transcript_exon_variant	Exon 10 of 10	2		ENSP00000457910.1
BCO1	ENST00000563804.5 link	n.*1246G>A		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000457910.1

Frequencies

GnomAD3 genomes

AF:

0.00623

AC:

948

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00720

GnomAD2 exomes

AF:

0.00715

AC:

1795

AN:

250954

AF XY:

0.00775

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00506

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.00696

Gnomad OTH exome

AF:

0.00962

GnomAD4 exome

AF:

0.00657

AC:

9601

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

5034

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.00315

AC:

141

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00513

AC:

134

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0158

AC:

1366

AN:

86258

European-Finnish (FIN)

AF:

0.0130

AC:

689

AN:

52994

Middle Eastern (MID)

AF:

0.00937

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00612

AC:

6805

AN:

1111988

Other (OTH)

AF:

0.00641

AC:

387

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

518

1036

1553

2071

2589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<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:

0.00624

AC:

950

AN:

152250

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

487

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41546

American (AMR)

AF:

0.00575

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0114

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0143

AC:

152

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00816

AC:

555

AN:

68018

Other (OTH)

AF:

0.00712

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00636

Hom.:

Bravo

AF:

0.00496

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00743

AC:

902

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00735

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 13, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

0.17

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.18

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.34

MutationAssessor

Benign

1.8

PhyloP100

-0.93

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.79

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Benign

0.089

Polyphen

0.047

Vest4

0.16

MVP

0.55

MPC

0.094

ClinPred

0.0088

GERP RS

-1.4

Varity_R

0.33

gMVP

0.35

Mutation Taster

=100/0

polymorphism

(source)

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

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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