16-81245515-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_017429.3(BCO1):c.105T>C(p.Asn35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,986 control chromosomes in the GnomAD database, including 92,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12062 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80058 hom.)
• Consequence: BCO1 NM_017429.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-81245515-T-C is Benign according to our data. Variant chr16-81245515-T-C is described in ClinVar as [Benign]. Clinvar id is 1250161.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-81245515-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCO1	NM_017429.3	c.105T>C	p.Asn35=	synonymous_variant	2/11	ENST00000258168.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO1	ENST00000258168.7	c.105T>C	p.Asn35=	synonymous_variant	2/11	1	NM_017429.3	P1
BCO1	ENST00000564552.1	c.105T>C	p.Asn35=	synonymous_variant	2/4	2
BCO1	ENST00000563804.5	c.105T>C	p.Asn35=	synonymous_variant, NMD_transcript_variant	2/10	2

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58960 AN: 152042 Hom.: 12036 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.342

GnomAD3 exomes AF: 0.336 AC: 84386 AN: 251440 Hom.: 14642 AF XY: 0.330 AC XY: 44846 AN XY: 135898

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.362

Gnomad SAS exome AF: 0.272

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.328 AC: 479487 AN: 1461826 Hom.: 80058 Cov.: 45 AF XY: 0.326 AC XY: 237159 AN XY: 727216

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.388 AC: 59024 AN: 152160 Hom.: 12062 Cov.: 32 AF XY: 0.386 AC XY: 28751 AN XY: 74402

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.341

Alfa AF: 0.355 Hom.: 5144

Bravo AF: 0.391

Asia WGS AF: 0.323 AC: 1124 AN: 3478

EpiCase AF: 0.329

EpiControl AF: 0.324

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

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.013
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28370522; hg19: chr16-81279120; COSMIC: COSV50727977;