16-81262297-T-C

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.471+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,608,542 control chromosomes in the GnomAD database, including 33,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4242 hom., cov: 30)
  • Exomes 𝑓: 0.20 (29450 hom.)
• Consequence: BCO1 NM_017429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042527616).
• BP6: Variant 16-81262297-T-C is Benign according to our data. Variant chr16-81262297-T-C is described in ClinVar as [Benign]. Clinvar id is 1265199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCO1	NM_017429.3	c.471+14T>C		intron_variant		ENST00000258168.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO1	ENST00000258168.7	c.471+14T>C		intron_variant		1	NM_017429.3	P1
	ENST00000625028.1	n.1795A>G		non_coding_transcript_exon_variant	1/1
BCO1	ENST00000564552.1	c.485T>C	p.Met162Thr	missense_variant	4/4	2
BCO1	ENST00000563804.5	c.*95+14T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34749 AN: 151572 Hom.: 4242 Cov.: 30

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.211 AC: 53129 AN: 251368 Hom.: 5975 AF XY: 0.208 AC XY: 28239 AN XY: 135878

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.196 AC: 285880 AN: 1456852 Hom.: 29450 Cov.: 32 AF XY: 0.196 AC XY: 142152 AN XY: 725096

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.229 AC: 34768 AN: 151690 Hom.: 4242 Cov.: 30 AF XY: 0.226 AC XY: 16765 AN XY: 74108

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.232

Alfa AF: 0.177 Hom.: 738

Bravo AF: 0.242

TwinsUK AF: 0.203 AC: 751

ALSPAC AF: 0.198 AC: 763

ESP6500AA AF: 0.291 AC: 1281

ESP6500EA AF: 0.210 AC: 1805

ExAC AF: 0.212 AC: 25735

Asia WGS AF: 0.208 AC: 721 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.225

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_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	0.93
Dann	Benign	0.20
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0043	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	0.52	N
Sift	Pathogenic	0.0	D
Vest4		0.056
GERP RS		-3.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7500996; hg19: chr16-81295902; COSMIC: COSV50728581;