rs2725437

Positions:

• chr11-132911928-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012393.5(OPCML):​c.146+30998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,056 control chromosomes in the GnomAD database, including 7,834 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 (7834 hom., cov: 32)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.146+30998A>G		intron_variant		ENST00000524381.6	NP_001012393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.146+30998A>G		intron_variant		1	NM_001012393.5	ENSP00000434750

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45866 AN: 151938 Hom.: 7831 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.302 AC: 45884 AN: 152056 Hom.: 7834 Cov.: 32 AF XY: 0.296 AC XY: 22031 AN XY: 74324

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.291

Alfa AF: 0.362 Hom.: 7204

Bravo AF: 0.284

Asia WGS AF: 0.192 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs2725437; hg19: chr11-132781823;