rs477292

Variant names:

• chr6-154042252-C-T
• rs477292
• NM_000914.5:c.290+2418C>T

Variant summary

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

The NM_000914.5(OPRM1):​c.290+2418C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,064 control chromosomes in the GnomAD database, including 5,195 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 0.25 (5195 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.290+2418C>T		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.569+2418C>T		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.569+2418C>T		intron	N/A	NP_001272453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.290+2418C>T		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.569+2418C>T		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.476+2418C>T		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37918 AN: 151944 Hom.: 5177 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.250 AC: 37986 AN: 152064 Hom.: 5195 Cov.: 32 AF XY: 0.244 AC XY: 18157 AN XY: 74336

African (AFR) AF: 0.340 AC: 14101 AN: 41438

American (AMR) AF: 0.291 AC: 4450 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3472

East Asian (EAS) AF: 0.0467 AC: 242 AN: 5182

South Asian (SAS) AF: 0.0718 AC: 347 AN: 4832

European-Finnish (FIN) AF: 0.229 AC: 2424 AN: 10578

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14847 AN: 67974

Other (OTH) AF: 0.250 AC: 529 AN: 2116

Alfa AF: 0.251 Hom.: 633

Bravo AF: 0.261

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.014
DANN	Benign	0.55
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs477292; hg19: chr6-154363387;