Genetic Variant BCO1:c.323+259G>A (chr16-81260064-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017429.3(BCO1):c.323+259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 152,212 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.031 ( 217 hom., cov: 32)

Consequence

BCO1
NM_017429.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.108

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-81260064-G-A is Benign according to our data. Variant chr16-81260064-G-A is described in CliVar as Benign. Clinvar id is 1244506.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-81260064-G-A is described in CliVar as Benign. Clinvar id is 1244506.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-81260064-G-A is described in CliVar as Benign. Clinvar id is 1244506.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-81260064-G-A is described in CliVar as Benign. Clinvar id is 1244506.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-81260064-G-A is described in CliVar as Benign. Clinvar id is 1244506.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3 link	c.323+259G>A		intron_variant	Intron 3 of 10	ENST00000258168.7	NP_059125.2	Q9HAY6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCO1	ENST00000258168.7 link	c.323+259G>A	intron_variant	Intron 3 of 10	1	NM_017429.3	ENSP00000258168.2	Q9HAY6
BCO1	ENST00000564552.1 link	c.323+259G>A	intron_variant	Intron 3 of 3	2		ENSP00000455219.1	H3BPA2
BCO1	ENST00000563804.5 link	n.194-2072G>A	intron_variant	Intron 2 of 9	2		ENSP00000457910.1	H3BV18

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4696

AN:

152094

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00990

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.0201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0310

AC:

4716

AN:

152212

Hom.:

217

Cov.:

AF XY:

0.0297

AC XY:

2209

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.107

AC:

4435

AN:

41512

American (AMR)

AF:

0.00989

AC:

151

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00952

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000661

AC:

AN:

68036

Other (OTH)

AF:

0.0199

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

208

416

624

832

1040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.000439

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.1

(source)

DANN

Benign

0.55

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over