11-112175666-C-T

Variant names:

• chr11-112175666-C-T
• rs775490373
• NM_031938.7:c.65C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031938.7(BCO2):​c.65C>T​(p.Pro22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: BCO2 NM_031938.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.265
• Publications: 0 publications found

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]

ENSG00000255292 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035458922).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031938.7. 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
	BCO2	NM_031938.7	MANE Select	c.65C>T	p.Pro22Leu	missense	Exon 1 of 12	NP_114144.5
	BCO2	NM_001256398.3		c.65C>T	p.Pro22Leu	missense	Exon 1 of 10	NP_001243327.2	Q9BYV7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO2	ENST00000357685.11	TSL:1 MANE Select	c.65C>T	p.Pro22Leu	missense	Exon 1 of 12	ENSP00000350314.5	Q9BYV7-1
	BCO2	ENST00000361053.8	TSL:1	c.65C>T	p.Pro22Leu	missense	Exon 1 of 10	ENSP00000354338.4	Q9BYV7-5
	ENSG00000255292	ENST00000532699.1	TSL:3	n.*55+4992C>T		intron	N/A	ENSP00000456434.1	H3BRW5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251444 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461706 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111860

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	6.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.035	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.27
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.30
Sift	Benign	0.056	T
Sift4G	Uncertain	0.031	D
Polyphen		0.0	B
Vest4		0.055
MutPred		0.45		Gain of helix (P = 0.0078)
MVP		0.32
MPC		0.062
ClinPred		0.045	T
GERP RS		2.5
PromoterAI		-0.080	Neutral
Varity_R		0.025
gMVP		0.60
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs775490373; hg19: chr11-112046389;