11-132436788-A-AAC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001012393.5(OPCML):c.644-10_644-9insGT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 1,604,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: OPCML NM_001012393.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.402

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-132436788-A-AAC is Benign according to our data. Variant chr11-132436788-A-AAC is described in ClinVar as [Likely_benign]. Clinvar id is 3044942.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPCML	NM_001012393.5	c.644-10_644-9insGT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000524381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPCML	ENST00000524381.6	c.644-10_644-9insGT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001012393.5

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151668 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000819 AC: 119 AN: 1452752 Hom.: 0 Cov.: 32 AF XY: 0.0000983 AC XY: 71 AN XY: 722566

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.000229

Gnomad4 SAS exome AF: 0.000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000705

Gnomad4 OTH exome AF: 0.000167

GnomAD4 genome AF: 0.0000659 AC: 10 AN: 151776 Hom.: 0 Cov.: 33 AF XY: 0.0000405 AC XY: 3 AN XY: 74150

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000590

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

OPCML-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

This variant is classified as likely 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs145479085; hg19: chr11-132306682;