NM_017429.3:c.193+269_193+272delTTTT

Variant names:

• chr16-81245849-CTTTT-C
• rs1176582576
• NM_017429.3:c.193+269_193+272delTTTT

Variant summary

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

The NM_017429.3(BCO1):​c.193+269_193+272delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000075 (0 hom., cov: 0)
• Consequence: BCO1 NM_017429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• 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: 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+269_193+272delTTTT		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+247_193+250delTTTT		intron	N/A	ENSP00000258168.2	Q9HAY6
	BCO1	ENST00000891666.1		c.193+247_193+250delTTTT		intron	N/A	ENSP00000561725.1
	BCO1	ENST00000891665.1		c.193+247_193+250delTTTT		intron	N/A	ENSP00000561724.1

Frequencies

GnomAD3 genomes AF: 0.0000750 AC: 7 AN: 93366 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000363

Gnomad SAS AF: 0.000954

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000750 AC: 7 AN: 93390 Hom.: 0 Cov.: 0 AF XY: 0.0000480 AC XY: 2 AN XY: 41698

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

African (AFR) AF: 0.000151 AC: 4 AN: 26480

American (AMR) AF: 0.00 AC: 0 AN: 6512

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

East Asian (EAS) AF: 0.000364 AC: 1 AN: 2748

South Asian (SAS) AF: 0.000962 AC: 2 AN: 2078

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49470

Other (OTH) AF: 0.00 AC: 0 AN: 1210

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000197617), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

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: rs1176582576; hg19: chr16-81279454;