11-132435149-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The NM_001012393.5(OPCML):c.916+937G>A variant causes a intron change. The variant allele was found at a frequency of 0.00144 in 1,275,470 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (6 hom.)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.95

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP6: Variant 11-132435149-C-T is Benign according to our data. Variant chr11-132435149-C-T is described in ClinVar as [Benign]. Clinvar id is 3056745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00758 (1155/152336) while in subpopulation AFR AF= 0.0258 (1075/41590). AF 95% confidence interval is 0.0246. There are 13 homozygotes in gnomad4. There are 532 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPCML	NM_001012393.5	c.916+937G>A		intron_variant		ENST00000524381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPCML	ENST00000524381.6	c.916+937G>A		intron_variant		1	NM_001012393.5

Frequencies

GnomAD3 genomes AF: 0.00761 AC: 1158 AN: 152218 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00157 AC: 211 AN: 134532 Hom.: 4 AF XY: 0.00119 AC XY: 87 AN XY: 73266

Gnomad AFR exome AF: 0.0248

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000947

Gnomad OTH exome AF: 0.000965

GnomAD4 exome AF: 0.000607 AC: 682 AN: 1123134 Hom.: 6 Cov.: 24 AF XY: 0.000531 AC XY: 293 AN XY: 551908

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000330

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00758 AC: 1155 AN: 152336 Hom.: 13 Cov.: 33 AF XY: 0.00714 AC XY: 532 AN XY: 74478

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.00457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000387 Hom.: 0

Bravo AF: 0.00842

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

OPCML-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
Cadd	Uncertain	25
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs113899050; hg19: chr11-132305043;