rs483481

Positions:

• chr6-154142833-G-A
• chr6-154142833-G-C

Variant summary

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

The ENST00000337049.8(OPRM1):​c.1164+51361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,996 control chromosomes in the GnomAD database, including 12,151 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 0.40 (12151 hom., cov: 31)
• Consequence: OPRM1 ENST00000337049.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_001008503.3	c.1164+51361G>A		intron_variant			NP_001008503.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000337049.8	c.1164+51361G>A		intron_variant		1		ENSP00000338381
OPRM1	ENST00000524150.2	c.*250+51361G>A		intron_variant, NMD_transcript_variant		5		ENSP00000430575

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60006 AN: 151878 Hom.: 12135 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.395 AC: 60050 AN: 151996 Hom.: 12151 Cov.: 31 AF XY: 0.396 AC XY: 29405 AN XY: 74292

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.405

Alfa AF: 0.412 Hom.: 19387

Bravo AF: 0.402

Asia WGS AF: 0.293 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.085
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs483481; hg19: chr6-154463968;