6-154120391-A-G

Variant names:

• chr6-154120391-A-G
• rs658156
• NM_000914.5:c.*1670A>G

Variant summary

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

The NM_000914.5(OPRM1):​c.*1670A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,020 control chromosomes in the GnomAD database, including 34,301 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 0.67 (34301 hom., cov: 31)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.*1670A>G		3_prime_UTR	Exon 4 of 4	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.*1670A>G		3_prime_UTR	Exon 6 of 6	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.*1670A>G		3_prime_UTR	Exon 5 of 5	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.*1670A>G		3_prime_UTR	Exon 4 of 4	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000337049.8	TSL:1	c.1164+28919A>G		intron	N/A	ENSP00000338381.4	P35372-5
	OPRM1	ENST00000524150.2	TSL:5	n.*250+28919A>G		intron	N/A	ENSP00000430575.1	P35372-18

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101579 AN: 151902 Hom.: 34303 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.668 AC: 101610 AN: 152020 Hom.: 34301 Cov.: 31 AF XY: 0.675 AC XY: 50178 AN XY: 74332

African (AFR) AF: 0.614 AC: 25478 AN: 41476

American (AMR) AF: 0.732 AC: 11176 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2392 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4655 AN: 5182

South Asian (SAS) AF: 0.828 AC: 3984 AN: 4812

European-Finnish (FIN) AF: 0.688 AC: 7275 AN: 10578

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44403 AN: 67908

Other (OTH) AF: 0.706 AC: 1492 AN: 2112

Alfa AF: 0.563 Hom.: 1852

Bravo AF: 0.672

Asia WGS AF: 0.841 AC: 2916 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.6
DANN	Benign	0.77
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs658156;

hg19: chr6-154441526;