11-132925674-G-T

Variant names:

• chr11-132925674-G-T
• rs10894623
• NM_001012393.5:c.146+17252C>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.146+17252C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,102 control chromosomes in the GnomAD database, including 3,857 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 0.20 (3857 hom., cov: 32)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	NM_001012393.5	MANE Select	c.146+17252C>A		intron	N/A	NP_001012393.1
	OPCML	NM_001319103.2		c.167+17252C>A		intron	N/A	NP_001306032.1
	OPCML	NM_002545.5		c.167+17252C>A		intron	N/A	NP_002536.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	ENST00000524381.6	TSL:1 MANE Select	c.146+17252C>A		intron	N/A	ENSP00000434750.1
	OPCML	ENST00000331898.11	TSL:1	c.167+17252C>A		intron	N/A	ENSP00000330862.7
	OPCML	ENST00000374778.4	TSL:1	c.44+17252C>A		intron	N/A	ENSP00000363910.4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29681 AN: 151984 Hom.: 3857 Cov.: 32

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.195 AC: 29671 AN: 152102 Hom.: 3857 Cov.: 32 AF XY: 0.189 AC XY: 14056 AN XY: 74362

African (AFR) AF: 0.0535 AC: 2221 AN: 41518

American (AMR) AF: 0.158 AC: 2421 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3470

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4810

European-Finnish (FIN) AF: 0.200 AC: 2112 AN: 10566

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19966 AN: 67962

Other (OTH) AF: 0.204 AC: 432 AN: 2114

Alfa AF: 0.257 Hom.: 9008

Bravo AF: 0.184

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.82
PhyloP100		-0.81
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: rs10894623; hg19: chr11-132795569;