rs4379857

Variant names:

• chr11-133313709-G-A
• rs4379857
• NM_001012393.5:c.61+218555C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-133313709-G-A
• chr11-133313709-G-T

Variant summary

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

The NM_001012393.5(OPCML):​c.61+218555C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 152,120 control chromosomes in the GnomAD database, including 1,137 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 0.076 (1137 hom., cov: 32)
• Consequence: OPCML NM_001012393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.61+218555C>T		intron_variant	Intron 1 of 7	ENST00000524381.6	NP_001012393.1
OPCML	NM_001319104.4	c.-134+218555C>T		intron_variant	Intron 1 of 6		NP_001306033.1
OPCML	XM_006718846.4	c.61+218555C>T		intron_variant	Intron 1 of 7		XP_006718909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.61+218555C>T		intron_variant	Intron 1 of 7	1	NM_001012393.5	ENSP00000434750.1
OPCML	ENST00000529038.5	n.139+218555C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11566 AN: 152002 Hom.: 1130 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0761 AC: 11581 AN: 152120 Hom.: 1137 Cov.: 32 AF XY: 0.0806 AC XY: 5991 AN XY: 74346

African (AFR) AF: 0.0160 AC: 664 AN: 41538

American (AMR) AF: 0.217 AC: 3323 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.447 AC: 2290 AN: 5120

South Asian (SAS) AF: 0.0876 AC: 421 AN: 4806

European-Finnish (FIN) AF: 0.0693 AC: 734 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0554 AC: 3769 AN: 67994

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0606 Hom.: 322

Bravo AF: 0.0881

Asia WGS AF: 0.278 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		-0.21
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: rs4379857; hg19: chr11-133183604;