16-81264428-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.472-212A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,160 control chromosomes in the GnomAD database, including 3,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3538 hom., cov: 32)
• Consequence: BCO1 NM_017429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.640

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=-0.91).
• BP6: Variant 16-81264428-A-G is Benign according to our data. Variant chr16-81264428-A-G is described in ClinVar as [Benign]. Clinvar id is 1272760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCO1	NM_017429.3	c.472-212A>G		intron_variant		ENST00000258168.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO1	ENST00000258168.7	c.472-212A>G		intron_variant		1	NM_017429.3	P1
BCO1	ENST00000563804.5	c.*96-212A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29513 AN: 152042 Hom.: 3538 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.194 AC: 29500 AN: 152160 Hom.: 3538 Cov.: 32 AF XY: 0.194 AC XY: 14422 AN XY: 74382

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0961

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.190

Alfa AF: 0.226 Hom.: 998

Bravo AF: 0.177

Asia WGS AF: 0.109 AC: 379 AN: 3478

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	-0.91
Cadd	Benign	3.3
Dann	Benign	0.65

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: rs67054945; hg19: chr16-81298033;