16-81245849-CTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTT

Variant names:

• chr16-81245849-C-CTT
• rs1176582576
• NM_017429.3:c.193+271_193+272dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_017429.3(BCO1):​c.193+271_193+272dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0095 (139 hom., cov: 0)
• Consequence: BCO1 NM_017429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.889
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 887 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017429.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO1	NM_017429.3	MANE Select	c.193+271_193+272dupTT		intron	N/A	NP_059125.2	Q9HAY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO1	ENST00000258168.7	TSL:1 MANE Select	c.193+246_193+247insTT		intron	N/A	ENSP00000258168.2	Q9HAY6
	BCO1	ENST00000891666.1		c.193+246_193+247insTT		intron	N/A	ENSP00000561725.1
	BCO1	ENST00000891665.1		c.193+246_193+247insTT		intron	N/A	ENSP00000561724.1

Frequencies

GnomAD3 genomes AF: 0.00950 AC: 887 AN: 93364 Hom.: 139 Cov.: 0

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.00436

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.00294

Gnomad MID AF: 0.00862

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00950 AC: 887 AN: 93388 Hom.: 139 Cov.: 0 AF XY: 0.00859 AC XY: 358 AN XY: 41696

African (AFR) AF: 0.00181 AC: 48 AN: 26482

American (AMR) AF: 0.00691 AC: 45 AN: 6510

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 31 AN: 2732

East Asian (EAS) AF: 0.00437 AC: 12 AN: 2746

South Asian (SAS) AF: 0.0120 AC: 25 AN: 2078

European-Finnish (FIN) AF: 0.00294 AC: 4 AN: 1362

Middle Eastern (MID) AF: 0.00926 AC: 1 AN: 108

European-Non Finnish (NFE) AF: 0.0140 AC: 693 AN: 49472

Other (OTH) AF: 0.00248 AC: 3 AN: 1210

Alfa AF: 0.00414 Hom.: 177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1176582576; hg19: chr16-81279454;