Variant rs9479757 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000914.5(OPRM1):c.643+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,468,760 control chromosomes in the GnomAD database, including 6,303 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 0.10 ( 874 hom., cov: 32)

Exomes 𝑓: 0.088 ( 5429 hom. )

Consequence

OPRM1
NM_000914.5 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 1.48

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.643+31G>A		intron_variant		ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.643+31G>A		intron_variant		1	NM_000914.5	ENSP00000328264	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15459

AN:

152030

Hom.:

869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0746

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.0421

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.0925

GnomAD3 exomes

AF:

0.0848

AC:

19104

AN:

225208

Hom.:

936

AF XY:

0.0817

AC XY:

9920

AN XY:

121394

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.0838

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.0487

Gnomad SAS exome

AF:

0.0257

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.0910

Gnomad OTH exome

AF:

0.0819

GnomAD4 exome

AF:

0.0877

AC:

115481

AN:

1316612

Hom.:

5429

Cov.:

AF XY:

0.0856

AC XY:

56502

AN XY:

660018

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.0825

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.0404

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.0920

Gnomad4 OTH exome

AF:

0.0844

GnomAD4 genome

AF:

0.102

AC:

15493

AN:

152148

Hom.:

874

Cov.:

AF XY:

0.101

AC XY:

7542

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0745

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.0424

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.0944

Gnomad4 OTH

AF:

0.0916

Alfa

AF:

0.0976

Hom.:

195

Bravo

AF:

0.0993

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Tramadol response

Other:1

drug response, no assertion criteria provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 28, 2018

- 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

-0.83

CADD

Benign

5.6

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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