11-133251042-C-G

Variant names:

• chr11-133251042-C-G
• rs2078454
• NM_001012393.5:c.61+281222G>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001012393.5(OPCML):​c.61+281222G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 151,980 control chromosomes in the GnomAD database, including 1 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 0.0014 (1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High AC in GnomAd4 at 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.61+281222G>C		intron_variant	Intron 1 of 7	ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-134+281222G>C		intron_variant	Intron 1 of 6		NP_001306033.1
OPCML	XM_006718846.4	c.61+281222G>C		intron_variant	Intron 1 of 7		XP_006718909.1
OPCML	XM_047427032.1	c.-42+45982G>C		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>C		intron_variant	Intron 1 of 7	1	NM_001012393.5	ENSP00000434750.1
OPCML	ENST00000529038.5	n.139+281222G>C		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 209 AN: 151862 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00180

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00137 AC: 208 AN: 151980 Hom.: 1 Cov.: 31 AF XY: 0.00143 AC XY: 106 AN XY: 74276

Gnomad4 AFR AF: 0.000386

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00180

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00000673 Hom.: 3951

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.48

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;