NM_000914.5:c.1165-1189A>G

Variant names:

• chr6-154117494-A-G
• rs648893
• NM_000914.5:c.1165-1189A>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.1165-1189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,166 control chromosomes in the GnomAD database, including 2,980 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 0.18 (2980 hom., cov: 31)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 23 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 (NFE) allele frequency at 95% confidence interval = 0.247 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.1165-1189A>G		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.1444-1189A>G		intron	N/A	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.1444-1189A>G		intron	N/A	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.1165-1189A>G		intron	N/A	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000434900.6	TSL:1	c.1444-1189A>G		intron	N/A	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000337049.8	TSL:1	c.1164+26022A>G		intron	N/A	ENSP00000338381.4	P35372-5

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27440 AN: 152048 Hom.: 2978 Cov.: 31

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.180 AC: 27460 AN: 152166 Hom.: 2980 Cov.: 31 AF XY: 0.176 AC XY: 13083 AN XY: 74386

African (AFR) AF: 0.0765 AC: 3177 AN: 41536

American (AMR) AF: 0.180 AC: 2756 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3470

East Asian (EAS) AF: 0.0845 AC: 437 AN: 5174

South Asian (SAS) AF: 0.145 AC: 701 AN: 4822

European-Finnish (FIN) AF: 0.188 AC: 1988 AN: 10578

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17041 AN: 67992

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.208 Hom.: 1521

Bravo AF: 0.174

Asia WGS AF: 0.112 AC: 390 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	4.5
DANN	Benign	0.25
PhyloP100		-0.23
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: rs648893; hg19: chr6-154438629;