dbSNP rs1323040: OPRM1:c.-130A>G (chr6-154010889-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000434900.6(OPRM1):c.-130A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,317,428 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

OPRM1
ENST00000434900.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.255

Publications

4 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
OPRM1	NM_001145279.4 link	c.-130A>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	NP_001138751.1	P35372-10B8K2Q5
OPRM1	NM_001145280.4 link	c.-140A>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	NP_001138752.1	P35372-12B8K2Q5
OPRM1	NM_001145279.4 link	c.-130A>G	5_prime_UTR_variant	Exon 1 of 6	NP_001138751.1	P35372-10B8K2Q5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
OPRM1	ENST00000434900.6 link	c.-130A>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	ENSP00000394624.2	P35372-10
OPRM1	ENST00000520708.5 link	c.-140A>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	ENSP00000430876.1	P35372-12
OPRM1	ENST00000520282.5 link	c.-120A>G	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	ENSP00000430247.1	E7EW71

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000154

AC:

AN:

1165344

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

571124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25200

American (AMR)

AF:

0.000303

AC:

AN:

23098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16314

East Asian (EAS)

AF:

0.00

AC:

AN:

17392

South Asian (SAS)

AF:

0.00

AC:

AN:

71130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4548

European-Non Finnish (NFE)

AF:

0.0000116

AC:

AN:

948628

Other (OTH)

AF:

0.00

AC:

AN:

44336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41430

American (AMR)

AF:

0.0000655

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.98

(source)

DANN

Benign

0.73

PhyloP100

-0.26

PromoterAI

-0.0072

Neutral

(source)

Splicing

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

Publications

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rs1323040

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