rs570969

Positions:

• chr11-133121868-C-A
• chr11-133121868-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012393.5(OPCML):​c.62-178858G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,956 control chromosomes in the GnomAD database, including 18,340 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 0.48 (18340 hom., cov: 32)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPCML	NM_001012393.5	c.62-178858G>T		intron_variant		ENST00000524381.6
OPCML	NM_001319104.4	c.-134+410396G>T		intron_variant
OPCML	XM_006718846.4	c.62-178858G>T		intron_variant
OPCML	XM_047427032.1	c.-42+175156G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPCML	ENST00000524381.6	c.62-178858G>T		intron_variant		1	NM_001012393.5
OPCML	ENST00000529038.5	n.139+410396G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72780 AN: 151836 Hom.: 18332 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.479 AC: 72821 AN: 151956 Hom.: 18340 Cov.: 32 AF XY: 0.483 AC XY: 35838 AN XY: 74244

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.481

Alfa AF: 0.532 Hom.: 35659

Bravo AF: 0.474

Asia WGS AF: 0.564 AC: 1960 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs570969; hg19: chr11-132991763;