dbSNP rs4889294: BCO1:c.844-5T>C (chr16-81270154-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017429.3(BCO1):c.844-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,594 control chromosomes in the GnomAD database, including 143,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 10118 hom., cov: 31)

Exomes 𝑓: 0.42 ( 133593 hom. )

Consequence

BCO1
NM_017429.3 splice_region, intron

Scores

Splicing: ADA: 0.0008851

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.84

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-81270154-T-C is Benign according to our data. Variant chr16-81270154-T-C is described in ClinVar as [Benign]. Clinvar id is 1233865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81270154-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3 link	c.844-5T>C		splice_region_variant, intron_variant	Intron 6 of 10	ENST00000258168.7	NP_059125.2	Q9HAY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCO1	ENST00000258168.7 link	c.844-5T>C		splice_region_variant, intron_variant	Intron 6 of 10	1	NM_017429.3	ENSP00000258168.2		Q9HAY6
BCO1	ENST00000563804.5 link	n.*468-5T>C		splice_region_variant, intron_variant	Intron 5 of 9	2		ENSP00000457910.1		H3BV18

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49580

AN:

151908

Hom.:

10115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0917

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.358

GnomAD3 exomes

AF:

0.361

AC:

90398

AN:

250492

Hom.:

18333

AF XY:

0.367

AC XY:

49763

AN XY:

135468

show subpopulations

Gnomad AFR exome

AF:

0.0857

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.469

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.278

Gnomad FIN exome

AF:

0.404

Gnomad NFE exome

AF:

0.457

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.417

AC:

609654

AN:

1461568

Hom.:

133593

Cov.:

AF XY:

0.414

AC XY:

301385

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0766

Gnomad4 AMR exome

AF:

0.306

Gnomad4 ASJ exome

AF:

0.467

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.453

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.326

AC:

49570

AN:

152026

Hom.:

10118

Cov.:

AF XY:

0.322

AC XY:

23929

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0914

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.472

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.422

Hom.:

31030

Bravo

AF:

0.310

Asia WGS

AF:

0.176

AC:

613

AN:

3478

EpiCase

AF:

0.464

EpiControl

AF:

0.457

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

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

-0.83

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00089

dbscSNV1_RF

Benign

0.024

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