chr11-132529107-A-G

Variant names:

• chr11-132529107-A-G
• rs145182728
• NM_001012393.5:c.459T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001012393.5(OPCML):​c.459T>C​(p.Ile153Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000705 in 1,613,522 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00073 (2 hom.)
• Consequence: OPCML NM_001012393.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.596
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-132529107-A-G is Benign according to our data. Variant chr11-132529107-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3039059.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.596 with no splicing effect.
• BS2: High AC in GnomAd4 at 68 AD gene.

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.459T>C	p.Ile153Ile	synonymous	Exon 4 of 8	NP_001012393.1	Q14982-2
	OPCML	NM_001319103.2		c.480T>C	p.Ile160Ile	synonymous	Exon 3 of 8	NP_001306032.1	Q14982-4
	OPCML	NM_002545.5		c.480T>C	p.Ile160Ile	synonymous	Exon 3 of 7	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.459T>C	p.Ile153Ile	synonymous	Exon 4 of 8	ENSP00000434750.1	Q14982-2
	OPCML	ENST00000331898.11	TSL:1	c.480T>C	p.Ile160Ile	synonymous	Exon 3 of 7	ENSP00000330862.7	Q14982-1
	OPCML	ENST00000374778.4	TSL:1	c.357T>C	p.Ile119Ile	synonymous	Exon 4 of 8	ENSP00000363910.4	Q14982-3

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000447 AC: 112 AN: 250616 AF XY: 0.000428

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000786

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000732 AC: 1070 AN: 1461230 Hom.: 2 Cov.: 30 AF XY: 0.000702 AC XY: 510 AN XY: 726906

African (AFR) AF: 0.000120 AC: 4 AN: 33446

American (AMR) AF: 0.000336 AC: 15 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86168

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53408

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.000884 AC: 983 AN: 1111602

Other (OTH) AF: 0.000629 AC: 38 AN: 60370

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26 AN XY: 74472

African (AFR) AF: 0.000168 AC: 7 AN: 41586

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68006

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000640 Hom.: 0

Bravo AF: 0.000555

EpiCase AF: 0.000764

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	OPCML-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		0.60
Mutation Taster		=99/1	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: rs145182728; hg19: chr11-132399001; COSMIC: COSV105897753; COSMIC: COSV105897753;