rs11223249

Variant names:

• chr11-132854822-G-A
• rs11223249
• NM_001012393.5:c.146+88104C>T

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+88104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,142 control chromosomes in the GnomAD database, including 5,803 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 0.26 (5803 hom., cov: 33)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 1 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.146+88104C>T		intron_variant	Intron 2 of 7	ENST00000524381.6	NP_001012393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.146+88104C>T		intron_variant	Intron 2 of 7	1	NM_001012393.5	ENSP00000434750.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40240 AN: 152024 Hom.: 5782 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.265 AC: 40313 AN: 152142 Hom.: 5803 Cov.: 33 AF XY: 0.263 AC XY: 19562 AN XY: 74382

African (AFR) AF: 0.376 AC: 15616 AN: 41492

American (AMR) AF: 0.218 AC: 3334 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1343 AN: 5156

South Asian (SAS) AF: 0.243 AC: 1170 AN: 4824

European-Finnish (FIN) AF: 0.238 AC: 2521 AN: 10580

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14670 AN: 68004

Other (OTH) AF: 0.296 AC: 624 AN: 2106

Alfa AF: 0.239 Hom.: 5433

Bravo AF: 0.266

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.12
PhyloP100		-1.0
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: rs11223249; hg19: chr11-132724717;