rs9322445

Variant names:

• chr6-154041119-A-G
• rs9322445
• NM_000914.5:c.290+1285A>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.290+1285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,124 control chromosomes in the GnomAD database, including 1,537 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 0.14 (1537 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• 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 = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+1285A>G		intron_variant	Intron 1 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.290+1285A>G		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20907 AN: 152006 Hom.: 1536 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.137 AC: 20911 AN: 152124 Hom.: 1537 Cov.: 32 AF XY: 0.134 AC XY: 9973 AN XY: 74360

African (AFR) AF: 0.0979 AC: 4067 AN: 41524

American (AMR) AF: 0.116 AC: 1773 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3468

East Asian (EAS) AF: 0.0467 AC: 242 AN: 5180

South Asian (SAS) AF: 0.0423 AC: 204 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2065 AN: 10562

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11650 AN: 67974

Other (OTH) AF: 0.124 AC: 261 AN: 2108

Alfa AF: 0.154 Hom.: 244

Bravo AF: 0.130

Asia WGS AF: 0.0390 AC: 136 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.48
DANN	Benign	0.52
PhyloP100		-0.67
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: rs9322445; hg19: chr6-154362254;