Variant rs7501331 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.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. 13/20 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.

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, single submitter B:1

Conservation

PhyloP100: 2.13

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=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 id is 1253021.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 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.1136C>T	p.Ala379Val	missense_variant	8/11	ENST00000258168.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO1	ENST00000258168.7 linkuse as main transcript	c.1136C>T	p.Ala379Val	missense_variant	8/11	1	NM_017429.3	P1
BCO1	ENST00000563804.5 linkuse as main transcript	c.*760C>T		3_prime_UTR_variant, NMD_transcript_variant	7/10	2

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

GnomAD3 exomes

AF:

0.211

AC:

53074

AN:

251278

Hom.:

6072

AF XY:

0.216

AC XY:

29362

AN XY:

135820

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 SAS exome

AF:

0.196

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

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.148

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.178

AC:

27070

AN:

152120

Hom.:

3081

Cov.:

AF XY:

0.181

AC XY:

13452

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0448

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.214

Hom.:

5036

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.28

CADD

Benign

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

MutationTaster

Benign

1.0

P;P

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

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

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