11-132436788-AACAC-AAC

Variant names:

• chr11-132436788-AAC-A
• rs145479085
• NM_001012393.5:c.644-11_644-10delGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001012393.5(OPCML):​c.644-11_644-10delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,361,508 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	NM_001012393.5	MANE Select	c.644-11_644-10delGT		intron	N/A	NP_001012393.1	Q14982-2
	OPCML	NM_001319103.2		c.665-11_665-10delGT		intron	N/A	NP_001306032.1	Q14982-4
	OPCML	NM_002545.5		c.665-11_665-10delGT		intron	N/A	NP_002536.1	A8K0Y0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	ENST00000524381.6	TSL:1 MANE Select	c.644-11_644-10delGT		intron	N/A	ENSP00000434750.1	Q14982-2
	OPCML	ENST00000331898.11	TSL:1	c.665-11_665-10delGT		intron	N/A	ENSP00000330862.7	Q14982-1
	OPCML	ENST00000374778.4	TSL:1	c.542-11_542-10delGT		intron	N/A	ENSP00000363910.4	Q14982-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151590 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0135 AC: 2246 AN: 166776 AF XY: 0.0141

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.0133

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.0142

Gnomad OTH exome AF: 0.00865

GnomAD4 exome AF: 0.00332 AC: 4517 AN: 1361508 Hom.: 0 AF XY: 0.00375 AC XY: 2534 AN XY: 675128

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00459 AC: 141 AN: 30690

American (AMR) AF: 0.00767 AC: 306 AN: 39904

Ashkenazi Jewish (ASJ) AF: 0.00513 AC: 120 AN: 23382

East Asian (EAS) AF: 0.00596 AC: 207 AN: 34730

South Asian (SAS) AF: 0.00662 AC: 512 AN: 77324

European-Finnish (FIN) AF: 0.00658 AC: 314 AN: 47748

Middle Eastern (MID) AF: 0.00245 AC: 13 AN: 5302

European-Non Finnish (NFE) AF: 0.00256 AC: 2682 AN: 1047054

Other (OTH) AF: 0.00401 AC: 222 AN: 55374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151694 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74104

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67802

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0316 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs145479085; hg19: chr11-132306682; COSMIC: COSV59435468;