NM_000914.5:c.290+1050C>T

Variant names:

• chr6-154040884-C-T
• rs510769
• NM_000914.5:c.290+1050C>T

Variant summary

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

The NM_000914.5(OPRM1):​c.290+1050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,898 control chromosomes in the GnomAD database, including 4,824 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 0.25 (4824 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 53 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 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.290+1050C>T		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.569+1050C>T		intron	N/A	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.569+1050C>T		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.290+1050C>T		intron	N/A	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000434900.6	TSL:1	c.569+1050C>T		intron	N/A	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.476+1050C>T		intron	N/A	ENSP00000353598.5	L0E130

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37925 AN: 151792 Hom.: 4806 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.250 AC: 37965 AN: 151898 Hom.: 4824 Cov.: 32 AF XY: 0.246 AC XY: 18270 AN XY: 74260

African (AFR) AF: 0.242 AC: 10039 AN: 41402

American (AMR) AF: 0.296 AC: 4509 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3466

East Asian (EAS) AF: 0.140 AC: 727 AN: 5180

South Asian (SAS) AF: 0.124 AC: 599 AN: 4812

European-Finnish (FIN) AF: 0.260 AC: 2744 AN: 10534

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17719 AN: 67940

Other (OTH) AF: 0.252 AC: 530 AN: 2102

Alfa AF: 0.253 Hom.: 10227

Bravo AF: 0.255

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.56
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs510769; hg19: chr6-154362019;