16-81262297-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_017429.3(BCO1):​c.471+14T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 1,609,302 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: BCO1 NM_017429.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BS2: High AC in GnomAd4 at 20 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3	c.471+14T>G		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>G		intron_variant	Intron 4 of 10	1	NM_017429.3	ENSP00000258168.2
BCO1	ENST00000564552.1	c.485T>G	p.Met162Arg	missense_variant	Exon 4 of 4	2		ENSP00000455219.1
ENSG00000280182	ENST00000625028.1	n.1795A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
BCO1	ENST00000563804.5	n.*95+14T>G		intron_variant	Intron 3 of 9	2		ENSP00000457910.1

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 151640 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00371

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000358 AC: 90 AN: 251368 AF XY: 0.000339

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000473 AC: 69 AN: 1457544 Hom.: 1 Cov.: 32 AF XY: 0.0000469 AC XY: 34 AN XY: 725440

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00164 AC: 65 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108126

Other (OTH) AF: 0.0000332 AC: 2 AN: 60262

GnomAD4 genome AF: 0.000132 AC: 20 AN: 151758 Hom.: 0 Cov.: 30 AF XY: 0.000162 AC XY: 12 AN XY: 74148

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00372 AC: 19 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.00 Hom.: 1383

ExAC AF: 0.000338 AC: 41

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	0.77
DANN	Benign	0.31
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.0037	T
PhyloP100		0.012
PROVEAN	Benign	2.3	N
Sift	Pathogenic	0.0	D
Vest4		0.11
MVP		0.55
GERP RS		-3.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.73		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.73		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7500996; hg19: chr16-81295902;