16-81245849-CTTTTTTTTTTTTTTTT-CTTTTTT

Variant names:

• chr16-81245849-CTTTTTTTTTT-C
• rs1176582576
• NM_017429.3:c.193+263_193+272delTTTTTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_017429.3(BCO1):​c.193+263_193+272delTTTTTTTTTT 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 0.0058 (7 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00585 (546/93384) while in subpopulation AFR AF = 0.0186 (493/26478). AF 95% confidence interval is 0.0173. There are 7 homozygotes in GnomAd4. There are 251 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 546 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+263_193+272delTTTTTTTTTT		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+256delTTTTTTTTTT		intron	N/A	ENSP00000258168.2	Q9HAY6
	BCO1	ENST00000891666.1		c.193+247_193+256delTTTTTTTTTT		intron	N/A	ENSP00000561725.1
	BCO1	ENST00000891665.1		c.193+247_193+256delTTTTTTTTTT		intron	N/A	ENSP00000561724.1

Frequencies

GnomAD3 genomes AF: 0.00582 AC: 543 AN: 93360 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00431

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000954

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.000243

Gnomad OTH AF: 0.00750

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

GnomAD4 genome AF: 0.00585 AC: 546 AN: 93384 Hom.: 7 Cov.: 0 AF XY: 0.00602 AC XY: 251 AN XY: 41696

African (AFR) AF: 0.0186 AC: 493 AN: 26478

American (AMR) AF: 0.00430 AC: 28 AN: 6512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2732

East Asian (EAS) AF: 0.00 AC: 0 AN: 2748

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1360

Middle Eastern (MID) AF: 0.0185 AC: 2 AN: 108

European-Non Finnish (NFE) AF: 0.000243 AC: 12 AN: 49470

Other (OTH) AF: 0.00744 AC: 9 AN: 1210

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

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;