11-133021828-A-G

Variant names:

• chr11-133021828-A-G
• rs4936180
• NM_001012393.5:c.62-78818T>C

Variant summary

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

The NM_001012393.5(OPCML):​c.62-78818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,032 control chromosomes in the GnomAD database, including 34,049 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 0.66 (34049 hom., cov: 32)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	NM_001012393.5	MANE Select	c.62-78818T>C		intron	N/A	NP_001012393.1
	OPCML	NM_001319104.4		c.-133-364509T>C		intron	N/A	NP_001306033.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	ENST00000524381.6	TSL:1 MANE Select	c.62-78818T>C		intron	N/A	ENSP00000434750.1
	OPCML	ENST00000529038.5	TSL:5	n.140-364509T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100838 AN: 151916 Hom.: 34002 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.673

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.664 AC: 100941 AN: 152032 Hom.: 34049 Cov.: 32 AF XY: 0.668 AC XY: 49624 AN XY: 74306

African (AFR) AF: 0.755 AC: 31313 AN: 41456

American (AMR) AF: 0.756 AC: 11551 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2103 AN: 3468

East Asian (EAS) AF: 0.809 AC: 4168 AN: 5150

South Asian (SAS) AF: 0.552 AC: 2655 AN: 4814

European-Finnish (FIN) AF: 0.603 AC: 6364 AN: 10554

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.598 AC: 40680 AN: 67996

Other (OTH) AF: 0.670 AC: 1414 AN: 2110

Alfa AF: 0.581 Hom.: 3072

Bravo AF: 0.685

Asia WGS AF: 0.688 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.053
DANN	Benign	0.67
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4936180; hg19: chr11-132891723;