16-81245829-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017429.3(BCO1):c.193+226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 140,978 control chromosomes in the GnomAD database, including 12,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (12266 hom., cov: 26)
• Consequence: BCO1 NM_017429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.83

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-81245829-A-G is Benign according to our data. Variant chr16-81245829-A-G is described in ClinVar as [Benign]. Clinvar id is 1248615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCO1	NM_017429.3	c.193+226A>G		intron_variant		ENST00000258168.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO1	ENST00000258168.7	c.193+226A>G		intron_variant		1	NM_017429.3	P1
BCO1	ENST00000564552.1	c.193+226A>G		intron_variant		2
BCO1	ENST00000563804.5	c.193+226A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 57870 AN: 140884 Hom.: 12238 Cov.: 26

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.411 AC: 57936 AN: 140978 Hom.: 12266 Cov.: 26 AF XY: 0.412 AC XY: 27908 AN XY: 67788

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.359

Alfa AF: 0.371 Hom.: 1496

Bravo AF: 0.400

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	10
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs11645422; hg19: chr16-81279434;