rs2078454

chr11-133251042-C-Achr11-133251042-C-Gchr11-133251042-C-T

Variant summary

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

The NM_001012393.5(OPCML):c.61+281222G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,886 control chromosomes in the GnomAD database, including 7,313 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 0.28 (7313 hom., cov: 31)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPCML	NM_001012393.5	c.61+281222G>T		intron_variant		ENST00000524381.6
OPCML	NM_001319104.4	c.-134+281222G>T		intron_variant
OPCML	XM_006718846.4	c.61+281222G>T		intron_variant
OPCML	XM_047427032.1	c.-42+45982G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPCML	ENST00000524381.6	c.61+281222G>T		intron_variant		1	NM_001012393.5
OPCML	ENST00000529038.5	n.139+281222G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43107 AN: 151768 Hom.: 7312 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.284 AC: 43139 AN: 151886 Hom.: 7313 Cov.: 31 AF XY: 0.283 AC XY: 21030 AN XY: 74232

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0845

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.275

Alfa AF: 0.217 Hom.: 3951

Bravo AF: 0.293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.35
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2078454; hg19: chr11-133120937;