16-81262297-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017429.3(BCO1):​c.471+14T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06046298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3	c.471+14T>A		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>A		intron_variant	Intron 4 of 10	1	NM_017429.3	ENSP00000258168.2
BCO1	ENST00000564552.1	c.485T>A	p.Met162Lys	missense_variant	Exon 4 of 4	2		ENSP00000455219.1
ENSG00000280182	ENST00000625028.1	n.1795A>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
BCO1	ENST00000563804.5	n.*95+14T>A		intron_variant	Intron 3 of 9	2		ENSP00000457910.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 1383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	0.68
DANN	Benign	0.54
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.060	T
PhyloP100		0.012
PROVEAN	Benign	4.0	N
Sift	Pathogenic	0.0	D
Vest4		0.11
MVP		0.55
GERP RS		-3.8

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

Other links and lift over

dbSNP: rs7500996; hg19: chr16-81295902;