NM_031938.7:c.736+5A>C

Variant names:

• chr11-112194760-A-C
• rs7123686
• NM_031938.7:c.736+5A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031938.7(BCO2):​c.736+5A>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 0.355 in 1,554,594 control chromosomes in the GnomAD database, including 102,159 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11211 hom., cov: 31)
  • Exomes 𝑓: 0.35 (90948 hom.)
• Consequence: BCO2 NM_031938.7 splice_region, intron
• Scores: Splicing: ADA: 0.00007611
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO2	NM_031938.7	MANE Select	c.736+5A>C		splice_region intron	N/A	NP_114144.5
	BCO2	NM_001037290.4		c.634+5A>C		splice_region intron	N/A	NP_001032367.3
	BCO2	NM_001256397.3		c.634+5A>C		splice_region intron	N/A	NP_001243326.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCO2	ENST00000357685.11	TSL:1 MANE Select	c.736+5A>C		splice_region intron	N/A	ENSP00000350314.5
	BCO2	ENST00000438022.5	TSL:1	c.634+5A>C		splice_region intron	N/A	ENSP00000414843.1
	BCO2	ENST00000531169.5	TSL:1	c.634+5A>C		splice_region intron	N/A	ENSP00000437053.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57387 AN: 151818 Hom.: 11184 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.383 AC: 92849 AN: 242740 AF XY: 0.389

Gnomad AFR exome AF: 0.453

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.353 AC: 495007 AN: 1402658 Hom.: 90948 Cov.: 23 AF XY: 0.360 AC XY: 252090 AN XY: 700874

African (AFR) AF: 0.466 AC: 14750 AN: 31644

American (AMR) AF: 0.368 AC: 15529 AN: 42198

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 9309 AN: 25624

East Asian (EAS) AF: 0.437 AC: 17088 AN: 39118

South Asian (SAS) AF: 0.577 AC: 47984 AN: 83194

European-Finnish (FIN) AF: 0.262 AC: 13991 AN: 53324

Middle Eastern (MID) AF: 0.427 AC: 2417 AN: 5656

European-Non Finnish (NFE) AF: 0.331 AC: 352250 AN: 1063464

Other (OTH) AF: 0.371 AC: 21689 AN: 58436

GnomAD4 genome AF: 0.378 AC: 57453 AN: 151936 Hom.: 11211 Cov.: 31 AF XY: 0.379 AC XY: 28178 AN XY: 74256

African (AFR) AF: 0.454 AC: 18811 AN: 41406

American (AMR) AF: 0.369 AC: 5629 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3472

East Asian (EAS) AF: 0.473 AC: 2444 AN: 5164

South Asian (SAS) AF: 0.596 AC: 2868 AN: 4810

European-Finnish (FIN) AF: 0.258 AC: 2721 AN: 10562

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22537 AN: 67942

Other (OTH) AF: 0.387 AC: 819 AN: 2114

Alfa AF: 0.340 Hom.: 5878

Bravo AF: 0.385

Asia WGS AF: 0.553 AC: 1923 AN: 3478

EpiCase AF: 0.342

EpiControl AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.59
PhyloP100		0.34
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.080		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: rs7123686; hg19: chr11-112065483;