16-81245849-CTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr16-81245849-C-CTTTTTT
• rs1176582576
• NM_017429.3:c.193+267_193+272dupTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017429.3(BCO1):​c.193+267_193+272dupTTTTTT 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 0.000021 (0 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: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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+267_193+272dupTTTTTT		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+247insTTTTTT		intron	N/A	ENSP00000258168.2	Q9HAY6
	BCO1	ENST00000891666.1		c.193+246_193+247insTTTTTT		intron	N/A	ENSP00000561725.1
	BCO1	ENST00000891665.1		c.193+246_193+247insTTTTTT		intron	N/A	ENSP00000561724.1

Frequencies

GnomAD3 genomes AF: 0.0000214 AC: 2 AN: 93368 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000477

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000202

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000214 AC: 2 AN: 93368 Hom.: 0 Cov.: 0 AF XY: 0.0000240 AC XY: 1 AN XY: 41680

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26452

American (AMR) AF: 0.00 AC: 0 AN: 6490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2734

East Asian (EAS) AF: 0.00 AC: 0 AN: 2756

South Asian (SAS) AF: 0.000477 AC: 1 AN: 2096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 116

European-Non Finnish (NFE) AF: 0.0000202 AC: 1 AN: 49474

Other (OTH) AF: 0.00 AC: 0 AN: 1200

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1176582576;

hg19: chr16-81279454;