rs12209447

Positions:

• chr6-154039913-C-T

Variant summary

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

The NM_000914.5(OPRM1):​c.290+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 1,313,184 control chromosomes in the GnomAD database, including 1,611 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 0.031 (120 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1491 hom.)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.290+79C>T		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.290+79C>T		intron_variant		1	NM_000914.5	P1

Frequencies

GnomAD3 genomes AF: 0.0311 AC: 4725 AN: 152052 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.00841

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.0460 AC: 53429 AN: 1161014 Hom.: 1491 AF XY: 0.0466 AC XY: 26651 AN XY: 571486

Gnomad4 AFR exome AF: 0.00540

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.00896

Gnomad4 EAS exome AF: 0.0938

Gnomad4 SAS exome AF: 0.0525

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0475

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0310 AC: 4717 AN: 152170 Hom.: 120 Cov.: 32 AF XY: 0.0306 AC XY: 2275 AN XY: 74388

Gnomad4 AFR AF: 0.00838

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.0947

Gnomad4 SAS AF: 0.0551

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0436

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0332 Hom.: 15

Bravo AF: 0.0286

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.81

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: rs12209447; hg19: chr6-154361048;