11-112194751-A-C

Position:

• chr11-112194751-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031938.7(BCO2):​c.732A>C​(p.Pro244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,587,752 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (11 hom.)
• Consequence: BCO2 NM_031938.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45

Genes affected

BCO2 (HGNC:18503): (beta-carotene oxygenase 2) This gene encodes an enzyme which oxidizes carotenoids such as beta-carotene during the biosynthesis of vitamin A. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-112194751-A-C is Benign according to our data. Variant chr11-112194751-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642372.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.45 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCO2	NM_031938.7	c.732A>C	p.Pro244=	synonymous_variant	5/12	ENST00000357685.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCO2	ENST00000357685.11	c.732A>C	p.Pro244=	synonymous_variant	5/12	1	NM_031938.7	P2

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 291 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00275 AC: 670 AN: 243892 Hom.: 1 AF XY: 0.00308 AC XY: 406 AN XY: 131914

Gnomad AFR exome AF: 0.000502

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00358

Gnomad FIN exome AF: 0.00251

Gnomad NFE exome AF: 0.00393

Gnomad OTH exome AF: 0.00284

GnomAD4 exome AF: 0.00279 AC: 4007 AN: 1435460 Hom.: 11 Cov.: 27 AF XY: 0.00285 AC XY: 2037 AN XY: 715430

Gnomad4 AFR exome AF: 0.000399

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.00147

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00387

Gnomad4 FIN exome AF: 0.00296

Gnomad4 NFE exome AF: 0.00298

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.00175 AC XY: 130 AN XY: 74482

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00313

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00230 Hom.: 1

Bravo AF: 0.00180

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

BCO2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149790013; hg19: chr11-112065474;