rs1941212

Positions:

• chr11-133418440-T-C

Variant summary

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

The NM_001012393.5(OPCML):​c.61+113824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 985,222 control chromosomes in the GnomAD database, including 1,600 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 0.071 (1087 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (513 hom.)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976

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]

OPCML (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.61+113824A>G		intron_variant		ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-134+113824A>G		intron_variant			NP_001306033.1
OPCML	XM_006718846.4	c.61+113824A>G		intron_variant			XP_006718909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.61+113824A>G		intron_variant		1	NM_001012393.5	ENSP00000434750.1
OPCML	ENST00000529038.5	n.139+113824A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10717 AN: 152084 Hom.: 1074 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.00834 AC: 6946 AN: 833020 Hom.: 513 Cov.: 29 AF XY: 0.00802 AC XY: 3086 AN XY: 384684

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.0584

Gnomad4 SAS exome AF: 0.0240

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.00214

Gnomad4 OTH exome AF: 0.0206

GnomAD4 genome AF: 0.0708 AC: 10773 AN: 152202 Hom.: 1087 Cov.: 32 AF XY: 0.0697 AC XY: 5188 AN XY: 74432

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.0637

Gnomad4 SAS AF: 0.0254

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.00432

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0417 Hom.: 220

Bravo AF: 0.0786

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1941212; hg19: chr11-133288335;