rs609148

chr6-154109880-G-Achr6-154109880-G-T

Variant summary

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

The NM_000914.5(OPRM1):c.1165-8803G>A 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 150,546 control chromosomes in the GnomAD database, including 3,459 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 (3459 hom., cov: 29)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.1165-8803G>A		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.1165-8803G>A		intron_variant		1	NM_000914.5	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31159 AN: 150430 Hom.: 3456 Cov.: 29

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.207 AC: 31192 AN: 150546 Hom.: 3459 Cov.: 29 AF XY: 0.202 AC XY: 14809 AN XY: 73430

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0850

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.194

Alfa AF: 0.231 Hom.: 532

Bravo AF: 0.204

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.6
Dann	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs609148; hg19: chr6-154431015;