rs12190259

Positions:

• chr6-154036852-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000434900.6(OPRM1):​c.1-2309A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,808 control chromosomes in the GnomAD database, including 2,185 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 0.12 (2185 hom., cov: 32)
• Consequence: OPRM1 ENST00000434900.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_001145279.4	c.1-2309A>C		intron_variant			NP_001138751.1
OPRM1	NM_001145280.4	c.-11+25834A>C		intron_variant			NP_001138752.1
OPRM1	NM_001145281.3	c.47+26293A>C		intron_variant			NP_001138753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000434900.6	c.1-2309A>C		intron_variant		1		ENSP00000394624
OPRM1	ENST00000518759.5	c.47+26293A>C		intron_variant		1		ENSP00000430260
OPRM1	ENST00000520282.5	c.11-2559A>C		intron_variant		1		ENSP00000430247
OPRM1	ENST00000520708.5	c.-11+25834A>C		intron_variant		1		ENSP00000430876

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18087 AN: 151690 Hom.: 2180 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0933

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.119 AC: 18120 AN: 151808 Hom.: 2185 Cov.: 32 AF XY: 0.116 AC XY: 8603 AN XY: 74240

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.0475

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0928

Gnomad4 SAS AF: 0.0642

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0456

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0758 Hom.: 210

Bravo AF: 0.129

Asia WGS AF: 0.100 AC: 349 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.077
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12190259; hg19: chr6-154357987;