NM_000914.5:c.1165-12077T>C

Variant names:

• chr6-154106606-T-C
• rs681243
• NM_000914.5:c.1165-12077T>C

Variant summary

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

The NM_000914.5(OPRM1):​c.1165-12077T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,178 control chromosomes in the GnomAD database, including 33,064 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 0.65 (33064 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• 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=-0.92).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.1165-12077T>C		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.1444-12077T>C		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.1444-12077T>C		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.1165-12077T>C		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.1444-12077T>C		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000419506.6	TSL:1	c.1165-859T>C		intron	N/A	ENSP00000403549.2

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99579 AN: 152060 Hom.: 33067 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.655 AC: 99607 AN: 152178 Hom.: 33064 Cov.: 33 AF XY: 0.662 AC XY: 49252 AN XY: 74382

African (AFR) AF: 0.565 AC: 23474 AN: 41512

American (AMR) AF: 0.728 AC: 11137 AN: 15296

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

East Asian (EAS) AF: 0.898 AC: 4653 AN: 5180

South Asian (SAS) AF: 0.829 AC: 4000 AN: 4826

European-Finnish (FIN) AF: 0.687 AC: 7269 AN: 10576

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

European-Non Finnish (NFE) AF: 0.654 AC: 44461 AN: 67998

Other (OTH) AF: 0.695 AC: 1470 AN: 2116

Alfa AF: 0.656 Hom.: 13401

Bravo AF: 0.657

Asia WGS AF: 0.839 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		0.29
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: rs681243; hg19: chr6-154427741;