rs589046

chr6-154072003-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000914.5(OPRM1):c.291-17823C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,944 control chromosomes in the GnomAD database, including 9,446 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 0.33 (9446 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.291-17823C>T		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.291-17823C>T		intron_variant		1	NM_000914.5	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49868 AN: 151826 Hom.: 9409 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.329 AC: 49958 AN: 151944 Hom.: 9446 Cov.: 32 AF XY: 0.322 AC XY: 23932 AN XY: 74262

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.306

Alfa AF: 0.263 Hom.: 8427

Bravo AF: 0.346

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.5
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs589046; hg19: chr6-154393138;