Variant 16-81262175-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017429.3(BCO1):c.363C>A(p.Thr121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,613,826 control chromosomes in the GnomAD database, including 2,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 150 hom., cov: 31)

Exomes 𝑓: 0.052 ( 2273 hom. )

Consequence

BCO1
NM_017429.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.45

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 16-81262175-C-A is Benign according to our data. Variant chr16-81262175-C-A is described in ClinVar as [Benign]. Clinvar id is 1230730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCO1	NM_017429.3 linkuse as main transcript	c.363C>A	p.Thr121=	synonymous_variant	4/11	ENST00000258168.7	NP_059125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
BCO1	ENST00000258168.7 linkuse as main transcript	c.363C>A	p.Thr121=	synonymous_variant	4/11	1	NM_017429.3	ENSP00000258168	P1
	ENST00000625028.1 linkuse as main transcript	n.1917G>T		non_coding_transcript_exon_variant	1/1
BCO1	ENST00000564552.1 linkuse as main transcript	c.363C>A	p.Thr121=	synonymous_variant	4/4	2		ENSP00000455219
BCO1	ENST00000563804.5 linkuse as main transcript	c.233C>A	p.Pro78Gln	missense_variant, NMD_transcript_variant	3/10	2		ENSP00000457910

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5532

AN:

152124

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.0250

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0577

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0355

AC:

8922

AN:

251414

Hom.:

220

AF XY:

0.0361

AC XY:

4909

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00941

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0197

Gnomad FIN exome

AF:

0.0438

Gnomad NFE exome

AF:

0.0557

Gnomad OTH exome

AF:

0.0318

GnomAD4 exome

AF:

0.0519

AC:

75811

AN:

1461584

Hom.:

2273

Cov.:

AF XY:

0.0516

AC XY:

37486

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00747

Gnomad4 AMR exome

AF:

0.0168

Gnomad4 ASJ exome

AF:

0.0149

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0224

Gnomad4 FIN exome

AF:

0.0451

Gnomad4 NFE exome

AF:

0.0607

Gnomad4 OTH exome

AF:

0.0418

GnomAD4 genome

AF:

0.0363

AC:

5531

AN:

152242

Hom.:

150

Cov.:

AF XY:

0.0354

AC XY:

2635

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.0457

Gnomad4 NFE

AF:

0.0577

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0404

Hom.:

Bravo

AF:

0.0326

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0519

EpiControl

AF:

0.0521

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

BCO1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.67

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.67

Position offset: 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