Variant rs2075572 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.644-83G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,267,934 control chromosomes in the GnomAD database, including 217,224 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 0.55 ( 23380 hom., cov: 32)

Exomes 𝑓: 0.59 ( 193844 hom. )

Consequence

OPRM1
NM_000914.5 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.929

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:

OPRM1 (HGNC:):

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 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.644-83G>C		intron_variant		ENST00000330432.12	NP_000905.3	P35372-1G8XRH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.644-83G>C		intron_variant		1	NM_000914.5	ENSP00000328264.7		P35372-1

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83217

AN:

151954

Hom.:

23389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.791

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.574

GnomAD4 exome

AF:

0.585

AC:

653323

AN:

1115862

Hom.:

193844

AF XY:

0.589

AC XY:

328248

AN XY:

556928

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.532

Gnomad4 ASJ exome

AF:

0.601

Gnomad4 EAS exome

AF:

0.782

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.570

Gnomad4 OTH exome

AF:

0.590

GnomAD4 genome

AF:

0.547

AC:

83220

AN:

152072

Hom.:

23380

Cov.:

AF XY:

0.554

AC XY:

41208

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.441

Gnomad4 AMR

AF:

0.547

Gnomad4 ASJ

AF:

0.596

Gnomad4 EAS

AF:

0.792

Gnomad4 SAS

AF:

0.748

Gnomad4 FIN

AF:

0.610

Gnomad4 NFE

AF:

0.566

Gnomad4 OTH

AF:

0.574

Alfa

AF:

0.426

Hom.:

1248

Bravo

AF:

0.538

Asia WGS

AF:

0.737

AC:

2562

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

-0.91

CADD

Benign

0.22

DANN

Benign

0.40

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