rs12205732

Variant names:

• chr6-154037798-G-A
• rs12205732
• ENST00000434900.6:c.1-1363G>A

Variant summary

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

The NM_001145279.4(OPRM1):​c.1-1363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 152,040 control chromosomes in the GnomAD database, including 371 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 0.059 (371 hom., cov: 32)
• Consequence: OPRM1 NM_001145279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 10 publications found

Genes affected

OPRM1 (HGNC:8156): (opioid receptor mu 1) This gene encodes one of at least three opioid receptors in humans; the mu opioid receptor (MOR). The MOR is the principal target of endogenous opioid peptides and opioid analgesic agents such as beta-endorphin and enkephalins. The MOR also has an important role in dependence to other drugs of abuse, such as nicotine, cocaine, and alcohol via its modulation of the dopamine system. The NM_001008503.2:c.118A>G allele has been associated with opioid and alcohol addiction and variations in pain sensitivity but evidence for it having a causal role is conflicting. Multiple transcript variants encoding different isoforms have been found for this gene. Though the canonical MOR belongs to the superfamily of 7-transmembrane-spanning G-protein-coupled receptors some isoforms of this gene have only 6 transmembrane domains. [provided by RefSeq, Oct 2013]

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 (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_001145279.4	c.1-1363G>A		intron_variant	Intron 1 of 5		NP_001138751.1
OPRM1	NM_001145281.3	c.47+27239G>A		intron_variant	Intron 1 of 3		NP_001138753.1
OPRM1	NM_001145280.4	c.-11+26780G>A		intron_variant	Intron 1 of 3		NP_001138752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000434900.6	c.1-1363G>A		intron_variant	Intron 1 of 5	1		ENSP00000394624.2
OPRM1	ENST00000518759.5	c.47+27239G>A		intron_variant	Intron 1 of 3	1		ENSP00000430260.1
OPRM1	ENST00000520708.5	c.-11+26780G>A		intron_variant	Intron 1 of 3	1		ENSP00000430876.1
OPRM1	ENST00000520282.5	c.11-1613G>A		intron_variant	Intron 1 of 2	1		ENSP00000430247.1

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9018 AN: 151920 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.00895

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.0572

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0594 AC: 9026 AN: 152040 Hom.: 371 Cov.: 32 AF XY: 0.0585 AC XY: 4352 AN XY: 74336

African (AFR) AF: 0.106 AC: 4418 AN: 41506

American (AMR) AF: 0.0246 AC: 376 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00895 AC: 31 AN: 3464

East Asian (EAS) AF: 0.0931 AC: 481 AN: 5164

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4820

European-Finnish (FIN) AF: 0.0298 AC: 315 AN: 10584

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2976 AN: 67894

Other (OTH) AF: 0.0431 AC: 91 AN: 2110

Alfa AF: 0.0477 Hom.: 131

Bravo AF: 0.0616

Asia WGS AF: 0.0750 AC: 264 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.61
PhyloP100		-0.11
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: rs12205732; hg19: chr6-154358933;