dbSNP rs606545: OPRM1:c.*19G>A (chr6-154110430-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145282.2(OPRM1):c.*19G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,457,050 control chromosomes in the GnomAD database, including 37,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.21 ( 3500 hom., cov: 30)

Exomes 𝑓: 0.22 ( 34254 hom. )

Consequence

OPRM1
NM_001145282.2 3_prime_UTR

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.715

Variant links:

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]

OPRM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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 rank	MANE	Protein	UniProt
OPRM1	NM_000914.5 link	c.1165-8253G>A		intron_variant	Intron 3 of 3	ENST00000330432.12	NP_000905.3	P35372-1G8XRH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 link	c.1165-8253G>A		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7		P35372-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31475

AN:

151876

Hom.:

3497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0846

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.195

AC:

29701

AN:

152462

Hom.:

3191

AF XY:

0.196

AC XY:

15859

AN XY:

80952

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.0962

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.249

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.224

AC:

292139

AN:

1305056

Hom.:

34254

Cov.:

AF XY:

0.223

AC XY:

144950

AN XY:

648652

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.0858

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.241

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.207

AC:

31508

AN:

151994

Hom.:

3500

Cov.:

AF XY:

0.202

AC XY:

14983

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.0846

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.231

Hom.:

820

Bravo

AF:

0.204

Asia WGS

AF:

0.122

AC:

426

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Tramadol response

Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.7

DANN

Benign

0.39

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over