11-132909498-A-G

Variant names:

• chr11-132909498-A-G
• rs2725466
• NM_001012393.5:c.146+33428T>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.146+33428T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,998 control chromosomes in the GnomAD database, including 7,545 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 0.30 (7545 hom., cov: 33)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	NM_001012393.5	MANE Select	c.146+33428T>C		intron	N/A	NP_001012393.1
	OPCML	NM_001319103.2		c.167+33428T>C		intron	N/A	NP_001306032.1
	OPCML	NM_002545.5		c.167+33428T>C		intron	N/A	NP_002536.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	ENST00000524381.6	TSL:1 MANE Select	c.146+33428T>C		intron	N/A	ENSP00000434750.1
	OPCML	ENST00000331898.11	TSL:1	c.167+33428T>C		intron	N/A	ENSP00000330862.7
	OPCML	ENST00000374778.4	TSL:1	c.44+33428T>C		intron	N/A	ENSP00000363910.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45047 AN: 151880 Hom.: 7541 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.00676

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.296 AC: 45066 AN: 151998 Hom.: 7545 Cov.: 33 AF XY: 0.290 AC XY: 21524 AN XY: 74286

African (AFR) AF: 0.194 AC: 8030 AN: 41494

American (AMR) AF: 0.208 AC: 3178 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1431 AN: 3468

East Asian (EAS) AF: 0.00677 AC: 35 AN: 5168

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3467 AN: 10560

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26178 AN: 67904

Other (OTH) AF: 0.280 AC: 590 AN: 2106

Alfa AF: 0.357 Hom.: 16876

Bravo AF: 0.279

Asia WGS AF: 0.174 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.57
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2725466; hg19: chr11-132779393;