rs640070

Positions:

• chr11-132485442-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000524381.6(OPCML):​c.505+43619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 152,262 control chromosomes in the GnomAD database, including 87 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 0.027 (87 hom., cov: 32)
• Consequence: OPCML ENST00000524381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4097/152262) while in subpopulation NFE AF= 0.046 (3130/68016). AF 95% confidence interval is 0.0447. There are 87 homozygotes in gnomad4. There are 1816 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4097 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPCML	NM_001012393.5	c.505+43619A>G		intron_variant		ENST00000524381.6	NP_001012393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPCML	ENST00000524381.6	c.505+43619A>G		intron_variant		1	NM_001012393.5	ENSP00000434750

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4102 AN: 152144 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.00721

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0274

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

GnomAD4 genome AF: 0.0269 AC: 4097 AN: 152262 Hom.: 87 Cov.: 32 AF XY: 0.0244 AC XY: 1816 AN XY: 74448

Gnomad4 AFR AF: 0.00719

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0271

Alfa AF: 0.0359 Hom.: 27

Bravo AF: 0.0259

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs640070; hg19: chr11-132355336;