chr11-133251042-C-A

Variant names:

• chr11-133251042-C-A
• rs2078454
• NM_001012393.5:c.61+281222G>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.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
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.61+281222G>T		intron_variant	Intron 1 of 7	ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-134+281222G>T		intron_variant	Intron 1 of 6		NP_001306033.1
OPCML	XM_006718846.4	c.61+281222G>T		intron_variant	Intron 1 of 7		XP_006718909.1
OPCML	XM_047427032.1	c.-42+45982G>T		intron_variant	Intron 1 of 7		XP_047282988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.61+281222G>T		intron_variant	Intron 1 of 7	1	NM_001012393.5	ENSP00000434750.1
OPCML	ENST00000529038.5	n.139+281222G>T		intron_variant	Intron 1 of 6	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

African (AFR) AF: 0.475 AC: 19678 AN: 41390

American (AMR) AF: 0.216 AC: 3292 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3468

East Asian (EAS) AF: 0.0845 AC: 436 AN: 5162

South Asian (SAS) AF: 0.350 AC: 1683 AN: 4808

European-Finnish (FIN) AF: 0.206 AC: 2171 AN: 10524

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 14020 AN: 67960

Other (OTH) AF: 0.275 AC: 581 AN: 2114

Alfa AF: 0.232 Hom.: 11951

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
PhyloP100		-0.73
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: rs2078454; hg19: chr11-133120937;