11-133418524-G-A

Position:

• chr11-133418524-G-A

Variant summary

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

The NM_001012393.5(OPCML):​c.61+113740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 938,608 control chromosomes in the GnomAD database, including 1,560 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 (1090 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (470 hom.)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

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=-0.79).
• 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+113740C>T		intron_variant		ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-134+113740C>T		intron_variant			NP_001306033.1
OPCML	XM_006718846.4	c.61+113740C>T		intron_variant			XP_006718909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.61+113740C>T		intron_variant		1	NM_001012393.5	ENSP00000434750
OPCML	ENST00000529038.5	n.139+113740C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10718 AN: 152094 Hom.: 1077 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.0247

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.00818 AC: 6433 AN: 786396 Hom.: 470 Cov.: 13 AF XY: 0.00789 AC XY: 2878 AN XY: 364744

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.0350

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.0546

Gnomad4 SAS exome AF: 0.0241

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.00211

Gnomad4 OTH exome AF: 0.0201

GnomAD4 genome AF: 0.0708 AC: 10774 AN: 152212 Hom.: 1090 Cov.: 32 AF XY: 0.0697 AC XY: 5189 AN XY: 74442

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.0635

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.00432

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0470 Hom.: 107

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	-0.79
CADD	Benign	4.8
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1941211; hg19: chr11-133288419;