6-154119607-A-G

Variant names:

• chr6-154119607-A-G
• rs671531
• NM_000914.5:c.*886A>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.*886A>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 0.659 in 198,566 control chromosomes in the GnomAD database, including 44,032 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 (34325 hom., cov: 33)
  • Exomes 𝑓: 0.63 (9707 hom.)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 16 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=-0.82).
• 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.*886A>G		3_prime_UTR	Exon 4 of 4	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.*886A>G		3_prime_UTR	Exon 6 of 6	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.*886A>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.*886A>G		3_prime_UTR	Exon 4 of 4	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000337049.8	TSL:1	c.1164+28135A>G		intron	N/A	ENSP00000338381.4	P35372-5
	OPRM1	ENST00000524150.2	TSL:5	n.*250+28135A>G		intron	N/A	ENSP00000430575.1	P35372-18

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101646 AN: 151986 Hom.: 34327 Cov.: 33

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.627 AC: 29124 AN: 46462 Hom.: 9707 AF XY: 0.626 AC XY: 14250 AN XY: 22770

African (AFR) AF: 0.578 AC: 481 AN: 832

American (AMR) AF: 0.659 AC: 29 AN: 44

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 180 AN: 284

East Asian (EAS) AF: 0.859 AC: 122 AN: 142

South Asian (SAS) AF: 0.817 AC: 755 AN: 924

European-Finnish (FIN) AF: 0.714 AC: 10 AN: 14

Middle Eastern (MID) AF: 0.745 AC: 73 AN: 98

European-Non Finnish (NFE) AF: 0.622 AC: 26511 AN: 42654

Other (OTH) AF: 0.655 AC: 963 AN: 1470

GnomAD4 genome AF: 0.668 AC: 101679 AN: 152104 Hom.: 34325 Cov.: 33 AF XY: 0.675 AC XY: 50204 AN XY: 74358

African (AFR) AF: 0.616 AC: 25537 AN: 41486

American (AMR) AF: 0.731 AC: 11167 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2390 AN: 3470

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

South Asian (SAS) AF: 0.828 AC: 3992 AN: 4824

European-Finnish (FIN) AF: 0.687 AC: 7270 AN: 10586

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

European-Non Finnish (NFE) AF: 0.654 AC: 44424 AN: 67964

Other (OTH) AF: 0.704 AC: 1490 AN: 2116

Alfa AF: 0.660 Hom.: 39261

Bravo AF: 0.672

Asia WGS AF: 0.843 AC: 2930 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-0.13
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: rs671531; hg19: chr6-154440742;