16-81262297-T-C

Variant names:

• chr16-81262297-T-C
• rs7500996
• NM_017429.3:c.471+14T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0120
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• hereditary hypercarotenemia and vitamin A deficiency

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000280182 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
BCO1	NM_017429.3	c.471+14T>C		intron_variant	Intron 4 of 10	ENST00000258168.7	NP_059125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCO1	ENST00000258168.7	c.471+14T>C		intron_variant	Intron 4 of 10	1	NM_017429.3	ENSP00000258168.2
BCO1	ENST00000564552.1	c.485T>C	p.Met162Thr	missense_variant	Exon 4 of 4	2		ENSP00000455219.1
ENSG00000280182	ENST00000625028.1	n.1795A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
BCO1	ENST00000563804.5	n.*95+14T>C		intron_variant	Intron 3 of 9	2		ENSP00000457910.1

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

GnomAD2 exomes AF: 0.211 AC: 53129 AN: 251368 AF XY: 0.208

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 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

African (AFR) AF: 0.294 AC: 9815 AN: 33334

American (AMR) AF: 0.260 AC: 11606 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 6139 AN: 26094

East Asian (EAS) AF: 0.214 AC: 8470 AN: 39666

South Asian (SAS) AF: 0.171 AC: 14699 AN: 86172

European-Finnish (FIN) AF: 0.131 AC: 6967 AN: 53350

Middle Eastern (MID) AF: 0.279 AC: 1606 AN: 5758

European-Non Finnish (NFE) AF: 0.193 AC: 213975 AN: 1107538

Other (OTH) AF: 0.209 AC: 12603 AN: 60234

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

African (AFR) AF: 0.289 AC: 11940 AN: 41312

American (AMR) AF: 0.273 AC: 4167 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3464

East Asian (EAS) AF: 0.240 AC: 1225 AN: 5108

South Asian (SAS) AF: 0.187 AC: 899 AN: 4806

European-Finnish (FIN) AF: 0.120 AC: 1266 AN: 10546

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13703 AN: 67908

Other (OTH) AF: 0.232 AC: 488 AN: 2100

Alfa AF: 0.196 Hom.: 1383

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:2

Revision: criteria provided, multiple submitters, no conflicts

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_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
PhyloP100		0.012
PROVEAN	Benign	0.52	N
Sift	Pathogenic	0.0	D
Vest4		0.056
GERP RS		-3.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7500996; hg19: chr16-81295902; COSMIC: COSV50728581;