rs7118965

Positions:

• chr11-133504907-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001012393.5(OPCML):​c.61+27357T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,180 control chromosomes in the GnomAD database, including 4,348 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 0.22 (4348 hom., cov: 33)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.61+27357T>G		intron_variant		ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-134+27357T>G		intron_variant			NP_001306033.1
OPCML	XM_006718846.4	c.61+27357T>G		intron_variant			XP_006718909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.61+27357T>G		intron_variant		1	NM_001012393.5	ENSP00000434750
OPCML	ENST00000529038.5	n.139+27357T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33467 AN: 152062 Hom.: 4339 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.220 AC: 33509 AN: 152180 Hom.: 4348 Cov.: 33 AF XY: 0.217 AC XY: 16174 AN XY: 74400

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.192

Alfa AF: 0.183 Hom.: 1656

Bravo AF: 0.240

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7118965; hg19: chr11-133374802;