rs558025

Positions:

• chr6-154120830-A-G

Variant summary

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

The NM_000914.5(OPRM1):​c.*2109A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,170 control chromosomes in the GnomAD database, including 3,218 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 0.20 (3218 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

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=-0.88).
• 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/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.*2109A>G		3_prime_UTR_variant	4/4	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.*2109A>G		3_prime_UTR_variant	4/4	1	NM_000914.5	ENSP00000328264	P1
OPRM1	ENST00000337049.8	c.1164+29358A>G		intron_variant		1		ENSP00000338381
OPRM1	ENST00000524150.2	c.*250+29358A>G		intron_variant, NMD_transcript_variant		5		ENSP00000430575

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29729 AN: 152052 Hom.: 3216 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.196 AC: 29758 AN: 152170 Hom.: 3218 Cov.: 33 AF XY: 0.191 AC XY: 14193 AN XY: 74400

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.183

Alfa AF: 0.210 Hom.: 838

Bravo AF: 0.191

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs558025; hg19: chr6-154441965;