rs1164401455

Variant names:

• chr11-132529170-C-A
• rs1164401455
• NM_001012393.5:c.396G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-132529170-C-A
• chr11-132529170-C-G
• chr11-132529170-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001012393.5(OPCML):​c.396G>T​(p.Met132Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: OPCML NM_001012393.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0620
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.083358616).
• BS2: High AC in GnomAdExome4 at 7 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.396G>T	p.Met132Ile	missense	Exon 4 of 8	NP_001012393.1	Q14982-2
	OPCML	NM_001319103.2		c.417G>T	p.Met139Ile	missense	Exon 3 of 8	NP_001306032.1	Q14982-4
	OPCML	NM_002545.5		c.417G>T	p.Met139Ile	missense	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.396G>T	p.Met132Ile	missense	Exon 4 of 8	ENSP00000434750.1	Q14982-2
	OPCML	ENST00000331898.11	TSL:1	c.417G>T	p.Met139Ile	missense	Exon 3 of 7	ENSP00000330862.7	Q14982-1
	OPCML	ENST00000374778.4	TSL:1	c.294G>T	p.Met98Ile	missense	Exon 4 of 8	ENSP00000363910.4	Q14982-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248668 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1458608 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725408

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110294

Other (OTH) AF: 0.00 AC: 0 AN: 60264

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.083
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.83	N
PhyloP100		-0.062
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.11
Sift	Benign	0.29	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.33		Loss of loop (P = 0.1242)
MVP		0.23
MPC		0.86
ClinPred		0.69	D
GERP RS		5.9
Varity_R		0.17
gMVP		0.28
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1164401455; hg19: chr11-132399064; COSMIC: COSV100103316; COSMIC: COSV100103316;