rs554010904

Variant names:

• chr16-81245566-C-G
• rs554010904
• NM_017429.3:c.156C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-81245566-C-G
• chr16-81245566-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_017429.3(BCO1):​c.156C>G​(p.Asp52Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D52D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCO1 NM_017429.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.991

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3	c.156C>G	p.Asp52Glu	missense_variant	Exon 2 of 11	ENST00000258168.7	NP_059125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCO1	ENST00000258168.7	c.156C>G	p.Asp52Glu	missense_variant	Exon 2 of 11	1	NM_017429.3	ENSP00000258168.2
BCO1	ENST00000564552.1	c.156C>G	p.Asp52Glu	missense_variant	Exon 2 of 4	2		ENSP00000455219.1
BCO1	ENST00000563804.5	n.156C>G		non_coding_transcript_exon_variant	Exon 2 of 10	2		ENSP00000457910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.88	D;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.95	D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	3.6	H;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.99
MutPred		0.95		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.83
MPC		0.35
ClinPred		1.0	D
GERP RS		-0.88
Varity_R		0.81
gMVP		0.98

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: rs554010904; hg19: chr16-81279171;