Genetic Variant NM_001012393.5:c.379+117T>C (chr11-132656970-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001012393.5(OPCML):c.379+117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 1,482,142 control chromosomes in the GnomAD database, including 439,289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.81 ( 50026 hom., cov: 33)

Exomes 𝑓: 0.76 ( 389263 hom. )

Consequence

OPCML
NM_001012393.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.458

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPCML	NM_001012393.5 link	c.379+117T>C		intron_variant	Intron 3 of 7	ENST00000524381.6	NP_001012393.1	Q14982-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6 link	c.379+117T>C		intron_variant	Intron 3 of 7	1	NM_001012393.5	ENSP00000434750.1		Q14982-2

Frequencies

GnomAD3 genomes

AF:

0.805

AC:

122453

AN:

152106

Hom.:

49971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.940

Gnomad AMI

AF:

0.698

Gnomad AMR

AF:

0.763

Gnomad ASJ

AF:

0.725

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.758

Gnomad NFE

AF:

0.767

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.764

AC:

1015892

AN:

1329920

Hom.:

389263

AF XY:

0.763

AC XY:

493889

AN XY:

647716

show subpopulations

African (AFR)

AF:

0.948

AC:

28485

AN:

30040

American (AMR)

AF:

0.737

AC:

20467

AN:

27786

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

14713

AN:

20088

East Asian (EAS)

AF:

0.599

AC:

22064

AN:

36812

South Asian (SAS)

AF:

0.758

AC:

51231

AN:

67554

European-Finnish (FIN)

AF:

0.755

AC:

36093

AN:

47798

Middle Eastern (MID)

AF:

0.745

AC:

2810

AN:

3770

European-Non Finnish (NFE)

AF:

0.767

AC:

798458

AN:

1041224

Other (OTH)

AF:

0.758

AC:

41571

AN:

54848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

11808

23616

35424

47232

59040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20026

40052

60078

80104

100130

<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:

0.805

AC:

122562

AN:

152222

Hom.:

50026

Cov.:

AF XY:

0.802

AC XY:

59699

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.940

AC:

39072

AN:

41566

American (AMR)

AF:

0.762

AC:

11664

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

2517

AN:

3470

East Asian (EAS)

AF:

0.580

AC:

2998

AN:

5172

South Asian (SAS)

AF:

0.750

AC:

3615

AN:

4820

European-Finnish (FIN)

AF:

0.766

AC:

8112

AN:

10584

Middle Eastern (MID)

AF:

0.771

AC:

225

AN:

292

European-Non Finnish (NFE)

AF:

0.767

AC:

52125

AN:

68000

Other (OTH)

AF:

0.758

AC:

1599

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1169

2338

3507

4676

5845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.785

Hom.:

7362

Bravo

AF:

0.805

Asia WGS

AF:

0.696

AC:

2422

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.80

(source)

DANN

Benign

0.37

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over