rs7501331

Variant names:

• chr16-81280891-C-T
• rs7501331
• NM_017429.3:c.1136C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017429.3(BCO1):​c.1136C>T​(p.Ala379Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,611,860 control chromosomes in the GnomAD database, including 42,137 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (3081 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39056 hom.)
• Consequence: BCO1 NM_017429.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.13

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023401678).
• BP6: Variant 16-81280891-C-T is Benign according to our data. Variant chr16-81280891-C-T is described in ClinVar as [Benign]. Clinvar id is 1253021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCO1	NM_017429.3	c.1136C>T	p.Ala379Val	missense_variant	Exon 8 of 11	ENST00000258168.7	NP_059125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCO1	ENST00000258168.7	c.1136C>T	p.Ala379Val	missense_variant	Exon 8 of 11	1	NM_017429.3	ENSP00000258168.2
BCO1	ENST00000563804.5	n.*760C>T		non_coding_transcript_exon_variant	Exon 7 of 10	2		ENSP00000457910.1
BCO1	ENST00000563804.5	n.*760C>T		3_prime_UTR_variant	Exon 7 of 10	2		ENSP00000457910.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27050 AN: 152002 Hom.: 3074 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.211 AC: 53074 AN: 251278 Hom.: 6072 AF XY: 0.216 AC XY: 29362 AN XY: 135820

Gnomad AFR exome AF: 0.0441

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.196

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.226 AC: 329596 AN: 1459740 Hom.: 39056 Cov.: 32 AF XY: 0.225 AC XY: 163436 AN XY: 726252

Gnomad4 AFR exome AF: 0.0366

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.178 AC: 27070 AN: 152120 Hom.: 3081 Cov.: 32 AF XY: 0.181 AC XY: 13452 AN XY: 74358

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.185

Alfa AF: 0.214 Hom.: 5036

Bravo AF: 0.163

TwinsUK AF: 0.235 AC: 870

ALSPAC AF: 0.234 AC: 901

ESP6500AA AF: 0.0509 AC: 224

ESP6500EA AF: 0.233 AC: 2007

ExAC AF: 0.212 AC: 25720

Asia WGS AF: 0.195 AC: 679 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.226

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19103647) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Benign	0.15	T
Sift4G	Benign	0.21	T
Polyphen		0.12	B
Vest4		0.035
MPC		0.11
ClinPred		0.019	T
GERP RS		4.6
Varity_R		0.16
gMVP		0.58

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: rs7501331; hg19: chr16-81314496; COSMIC: COSV50728053;