rs504932

Variant names:

• chr6-154109334-A-G
• rs504932
• NM_000914.5:c.1165-9349A>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.1165-9349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,190 control chromosomes in the GnomAD database, including 3,481 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 0.21 (3481 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1165-9349A>G		intron_variant	Intron 3 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1165-9349A>G		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31409 AN: 152072 Hom.: 3478 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.207 AC: 31442 AN: 152190 Hom.: 3481 Cov.: 32 AF XY: 0.201 AC XY: 14960 AN XY: 74412

African (AFR) AF: 0.168 AC: 6986 AN: 41538

American (AMR) AF: 0.189 AC: 2895 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3472

East Asian (EAS) AF: 0.0845 AC: 439 AN: 5196

South Asian (SAS) AF: 0.146 AC: 704 AN: 4830

European-Finnish (FIN) AF: 0.188 AC: 1990 AN: 10578

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

European-Non Finnish (NFE) AF: 0.251 AC: 17028 AN: 67970

Other (OTH) AF: 0.193 AC: 407 AN: 2108

Alfa AF: 0.229 Hom.: 539

Bravo AF: 0.204

Asia WGS AF: 0.122 AC: 424 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.68
PhyloP100		1.0
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: rs504932; hg19: chr6-154430469;