NM_000914.5:c.*7689A>G

Variant names:

• chr6-154126410-A-G
• rs497315
• NM_000914.5:c.*7689A>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.*7689A>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 0.225 in 152,192 control chromosomes in the GnomAD database, including 4,006 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 0.22 (4006 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 6 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=-0.93).
• 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.*7689A>G		3_prime_UTR	Exon 4 of 4	NP_000905.3
	OPRM1	NM_001145279.4		c.*7689A>G		3_prime_UTR	Exon 6 of 6	NP_001138751.1
	OPRM1	NM_001285524.1		c.*7689A>G		3_prime_UTR	Exon 5 of 5	NP_001272453.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.*7689A>G		3_prime_UTR	Exon 4 of 4	ENSP00000328264.7
	OPRM1	ENST00000337049.8	TSL:1	c.1164+34938A>G		intron	N/A	ENSP00000338381.4
	OPRM1	ENST00000524150.2	TSL:5	n.*250+34938A>G		intron	N/A	ENSP00000430575.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34137 AN: 152072 Hom.: 4000 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.225 AC: 34176 AN: 152192 Hom.: 4006 Cov.: 32 AF XY: 0.219 AC XY: 16279 AN XY: 74416

African (AFR) AF: 0.233 AC: 9655 AN: 41516

American (AMR) AF: 0.193 AC: 2954 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3472

East Asian (EAS) AF: 0.0843 AC: 436 AN: 5172

South Asian (SAS) AF: 0.146 AC: 704 AN: 4826

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10594

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17036 AN: 68006

Other (OTH) AF: 0.195 AC: 412 AN: 2110

Alfa AF: 0.241 Hom.: 588

Bravo AF: 0.223

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.69
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: rs497315; hg19: chr6-154447545;