Variant 16-81268089-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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, single submitter B:1

Conservation

PhyloP100: -2.33

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 1293223.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-81268089-A-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
BCO1	NM_017429.3 linkuse as main transcript	c.801A>T	p.Arg267Ser	missense_variant	6/11	ENST00000258168.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO1	ENST00000258168.7 linkuse as main transcript	c.801A>T	p.Arg267Ser	missense_variant	6/11	1	NM_017429.3	P1
BCO1	ENST00000563804.5 linkuse as main transcript	c.*425A>T		3_prime_UTR_variant, NMD_transcript_variant	5/10	2

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

GnomAD3 exomes

AF:

0.358

AC:

89612

AN:

250002

Hom.:

17806

AF XY:

0.363

AC XY:

49118

AN XY:

135158

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 SAS exome

AF:

0.271

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

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.303

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.401

Gnomad4 NFE exome

AF:

0.445

Gnomad4 OTH exome

AF:

0.388

GnomAD4 genome

AF:

0.339

AC:

51319

AN:

151562

Hom.:

10103

Cov.:

AF XY:

0.334

AC XY:

24719

AN XY:

74030

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.469

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.364

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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

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

MutationTaster

Benign

1.0

P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over