chr11-133048569-G-T

Variant names:

• chr11-133048569-G-T
• rs11223339
• NM_001012393.5:c.62-105559C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012393.5(OPCML):​c.62-105559C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,128 control chromosomes in the GnomAD database, including 3,168 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 0.19 (3168 hom., cov: 33)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 3 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.62-105559C>A		intron_variant	Intron 1 of 7	ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-133-391250C>A		intron_variant	Intron 1 of 6		NP_001306033.1
OPCML	XM_006718846.4	c.62-105559C>A		intron_variant	Intron 1 of 7		XP_006718909.1
OPCML	XM_047427032.1	c.-41-105559C>A		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.62-105559C>A		intron_variant	Intron 1 of 7	1	NM_001012393.5	ENSP00000434750.1
OPCML	ENST00000529038.5	n.140-391250C>A		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29462 AN: 152012 Hom.: 3167 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.194 AC: 29469 AN: 152128 Hom.: 3168 Cov.: 33 AF XY: 0.197 AC XY: 14628 AN XY: 74382

African (AFR) AF: 0.132 AC: 5482 AN: 41490

American (AMR) AF: 0.284 AC: 4343 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3472

East Asian (EAS) AF: 0.261 AC: 1347 AN: 5168

South Asian (SAS) AF: 0.356 AC: 1714 AN: 4814

European-Finnish (FIN) AF: 0.176 AC: 1860 AN: 10584

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13259 AN: 68006

Other (OTH) AF: 0.218 AC: 460 AN: 2112

Alfa AF: 0.203 Hom.: 4846

Bravo AF: 0.200

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		0.079
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: rs11223339; hg19: chr11-132918464;