Genetic Variant OPCML:c.916+937G>A (chr11-132435149-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4BP6BS1BS2

The NM_001012393.5(OPCML):c.916+937G>A variant causes a intron change. The variant allele was found at a frequency of 0.00144 in 1,275,470 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0076 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 6 hom. )

Consequence

OPCML
NM_001012393.5 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.95

Publications

0 publications found

Variant links:

Genes affected

OPCML (HGNC:8143): (opioid binding protein/cell adhesion molecule like) This gene encodes a member of the IgLON subfamily in the immunoglobulin protein superfamily of proteins. The encoded preprotein is proteolytically processed to generate the mature protein. This protein is localized in the plasma membrane and may have an accessory role in opioid receptor function. This gene has an ortholog in rat and bovine. The opioid binding-cell adhesion molecule encoded by the rat gene binds opioid alkaloids in the presence of acidic lipids, exhibits selectivity for mu ligands and acts as a GPI-anchored protein. Since the encoded protein is highly conserved in species during evolution, it may have a fundamental role in mammalian systems. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

OPCML links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.15).

BP6

Variant 11-132435149-C-T is Benign according to our data. Variant chr11-132435149-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056745.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00758 (1155/152336) while in subpopulation AFR AF = 0.0258 (1075/41590). AF 95% confidence interval is 0.0246. There are 13 homozygotes in GnomAd4. There are 532 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1155 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPCML	NM_001012393.5	MANE Select	c.916+937G>A	intron	N/A	NP_001012393.1	Q14982-2
OPCML	NM_001319103.2		c.964+10G>A	intron	N/A	NP_001306032.1	Q14982-4
OPCML	NM_002545.5		c.937+937G>A	intron	N/A	NP_002536.1	A8K0Y0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPCML	ENST00000524381.6	TSL:1 MANE Select	c.916+937G>A	intron	N/A	ENSP00000434750.1	Q14982-2
OPCML	ENST00000331898.11	TSL:1	c.937+937G>A	intron	N/A	ENSP00000330862.7	Q14982-1
OPCML	ENST00000374778.4	TSL:1	c.814+937G>A	intron	N/A	ENSP00000363910.4	Q14982-3

Frequencies

GnomAD3 genomes

AF:

0.00761

AC:

1158

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00157

AC:

211

AN:

134532

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.00172

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000947

Gnomad OTH exome

AF:

0.000965

GnomAD4 exome

AF:

0.000607

AC:

682

AN:

1123134

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

293

AN XY:

551908

show subpopulations

African (AFR)

AF:

0.0225

AC:

541

AN:

24098

American (AMR)

AF:

0.00184

AC:

AN:

28246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15848

East Asian (EAS)

AF:

0.00

AC:

AN:

12782

South Asian (SAS)

AF:

0.00

AC:

AN:

75904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13058

Middle Eastern (MID)

AF:

0.000687

AC:

AN:

4368

European-Non Finnish (NFE)

AF:

0.0000330

AC:

AN:

907760

Other (OTH)

AF:

0.00136

AC:

AN:

41070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

118

147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00758

AC:

1155

AN:

152336

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

532

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0258

AC:

1075

AN:

41590

American (AMR)

AF:

0.00457

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00842

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

OPCML-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Benign

0.67

PhyloP100

4.0

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over