chr11-133041206-A-G

Variant names:

• chr11-133041206-A-G
• rs11223336
• NM_001012393.5:c.62-98196T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012393.5(OPCML):​c.62-98196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,208 control chromosomes in the GnomAD database, including 1,332 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 0.12 (1332 hom., cov: 32)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.62-98196T>C		intron_variant	Intron 1 of 7	ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-133-383887T>C		intron_variant	Intron 1 of 6		NP_001306033.1
OPCML	XM_006718846.4	c.62-98196T>C		intron_variant	Intron 1 of 7		XP_006718909.1
OPCML	XM_047427032.1	c.-41-98196T>C		intron_variant	Intron 1 of 7		XP_047282988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.62-98196T>C		intron_variant	Intron 1 of 7	1	NM_001012393.5	ENSP00000434750.1
OPCML	ENST00000529038.5	n.140-383887T>C		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18910 AN: 152090 Hom.: 1331 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18915 AN: 152208 Hom.: 1332 Cov.: 32 AF XY: 0.128 AC XY: 9533 AN XY: 74426

African (AFR) AF: 0.142 AC: 5901 AN: 41514

American (AMR) AF: 0.180 AC: 2749 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1140 AN: 5180

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4818

European-Finnish (FIN) AF: 0.113 AC: 1193 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0949 AC: 6458 AN: 68020

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.101 Hom.: 1761

Bravo AF: 0.126

Asia WGS AF: 0.225 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11223336; hg19: chr11-132911101;