dbSNP rs17181352: OPRM1:c.*725A>G (chr6-154119446-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000914.5(OPRM1):c.*725A>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 0.000298 in 985,388 control chromosomes in the GnomAD database, including 3 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 0.0010 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

OPRM1
NM_000914.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.257

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00103 (157/152294) while in subpopulation EAS AF = 0.0257 (133/5172). AF 95% confidence interval is 0.0222. There are 2 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5 link	c.*725A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000330432.12	NP_000905.3	P35372-1G8XRH5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPRM1	ENST00000330432.12 link	c.*725A>G	3_prime_UTR_variant	Exon 4 of 4	1	NM_000914.5	ENSP00000328264.7	P35372-1
OPRM1	ENST00000337049.8 link	c.1164+27974A>G	intron_variant	Intron 3 of 3	1		ENSP00000338381.4	P35372-5
OPRM1	ENST00000524150.2 link	n.*250+27974A>G	intron_variant	Intron 2 of 2	5		ENSP00000430575.1	P35372-18

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0257

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.000164

AC:

137

AN:

833094

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

384702

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15786

American (AMR)

AF:

0.00102

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5152

East Asian (EAS)

AF:

0.0234

AC:

AN:

3630

South Asian (SAS)

AF:

0.000122

AC:

AN:

16460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

276

Middle Eastern (MID)

AF:

0.000617

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.00000263

AC:

AN:

761888

Other (OTH)

AF:

0.00169

AC:

AN:

27298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152294

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41582

American (AMR)

AF:

0.000262

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0257

AC:

133

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000945

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.36

(source)

DANN

Benign

0.65

PhyloP100

-0.26

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over