16-81259602-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017429.3(BCO1):c.194-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00702 in 1,601,930 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (300 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (279 hom.)
• Consequence: BCO1 NM_017429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-81259602-A-G is Benign according to our data. Variant chr16-81259602-A-G is described in ClinVar as [Benign]. Clinvar id is 1287583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCO1	NM_017429.3	c.194-74A>G		intron_variant		ENST00000258168.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO1	ENST00000258168.7	c.194-74A>G		intron_variant		1	NM_017429.3	P1
BCO1	ENST00000564552.1	c.194-74A>G		intron_variant		2
BCO1	ENST00000563804.5	c.194-2534A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5387 AN: 152228 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0253

GnomAD4 exome AF: 0.00402 AC: 5832 AN: 1449584 Hom.: 279 AF XY: 0.00345 AC XY: 2491 AN XY: 721286

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.00554

Gnomad4 ASJ exome AF: 0.00918

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000364

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000284

Gnomad4 OTH exome AF: 0.00894

GnomAD4 genome AF: 0.0355 AC: 5406 AN: 152346 Hom.: 300 Cov.: 32 AF XY: 0.0340 AC XY: 2530 AN XY: 74508

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0210 Hom.: 19

Bravo AF: 0.0392

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.6
Dann	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs76073106; hg19: chr16-81293207;