NM_017429.3:c.844-5T>C

Variant names:

• chr16-81270154-T-C
• rs4889294
• NM_017429.3:c.844-5T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017429.3(BCO1):​c.844-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,594 control chromosomes in the GnomAD database, including 143,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (10118 hom., cov: 31)
  • Exomes 𝑓: 0.42 (133593 hom.)
• Consequence: BCO1 NM_017429.3 splice_region, intron
• Scores: Splicing: ADA: 0.0008851
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.84
• Publications: 27 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-81270154-T-C is Benign according to our data. Variant chr16-81270154-T-C is described in ClinVar as Benign. ClinVar VariationId is 1233865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

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.844-5T>C		splice_region 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.844-5T>C		splice_region intron	N/A	ENSP00000258168.2	Q9HAY6
	BCO1	ENST00000891666.1		c.844-5T>C		splice_region intron	N/A	ENSP00000561725.1
	BCO1	ENST00000891665.1		c.844-5T>C		splice_region intron	N/A	ENSP00000561724.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49580 AN: 151908 Hom.: 10115 Cov.: 31

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.361 AC: 90398 AN: 250492 AF XY: 0.367

Gnomad AFR exome AF: 0.0857

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.404

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.417 AC: 609654 AN: 1461568 Hom.: 133593 Cov.: 54 AF XY: 0.414 AC XY: 301385 AN XY: 727122

African (AFR) AF: 0.0766 AC: 2565 AN: 33480

American (AMR) AF: 0.306 AC: 13695 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 12191 AN: 26130

East Asian (EAS) AF: 0.145 AC: 5770 AN: 39700

South Asian (SAS) AF: 0.283 AC: 24389 AN: 86250

European-Finnish (FIN) AF: 0.412 AC: 22012 AN: 53376

Middle Eastern (MID) AF: 0.411 AC: 2365 AN: 5758

European-Non Finnish (NFE) AF: 0.453 AC: 503127 AN: 1111774

Other (OTH) AF: 0.390 AC: 23540 AN: 60378

GnomAD4 genome AF: 0.326 AC: 49570 AN: 152026 Hom.: 10118 Cov.: 31 AF XY: 0.322 AC XY: 23929 AN XY: 74294

African (AFR) AF: 0.0914 AC: 3791 AN: 41484

American (AMR) AF: 0.343 AC: 5232 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1637 AN: 3466

East Asian (EAS) AF: 0.141 AC: 727 AN: 5158

South Asian (SAS) AF: 0.271 AC: 1304 AN: 4810

European-Finnish (FIN) AF: 0.399 AC: 4215 AN: 10574

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31356 AN: 67948

Other (OTH) AF: 0.355 AC: 750 AN: 2114

Alfa AF: 0.403 Hom.: 41506

Bravo AF: 0.310

Asia WGS AF: 0.176 AC: 613 AN: 3478

EpiCase AF: 0.464

EpiControl AF: 0.457

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.57
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00089
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.070		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: rs4889294; hg19: chr16-81303759; COSMIC: COSV50729530;