Variant 6-154246729-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4BA1

The ENST00000337049.8(OPRM1):c.1201C>T(p.Arg401Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,613,866 control chromosomes in the GnomAD database, including 3,808 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 0.048 ( 253 hom., cov: 31)

Exomes 𝑓: 0.066 ( 3555 hom. )

Consequence

OPRM1
ENST00000337049.8 stop_gained

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -5.05

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:

IPCEF1 (HGNC:21204): (interaction protein for cytohesin exchange factors 1) Predicted to enable peroxidase activity. Predicted to be involved in response to oxidative stress. Predicted to be located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IPCEF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM4

Stoplost variant in ENST00000337049.8 Downstream stopcodon found after 434 codons.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPCEF1	NM_001130700.2 linkuse as main transcript	c.108G>A	p.Ser36=	synonymous_variant	5/12	ENST00000367220.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPCEF1	ENST00000367220.9 linkuse as main transcript	c.108G>A	p.Ser36=	synonymous_variant	5/12	2	NM_001130700.2	A2	Q8WWN9-2

Frequencies

GnomAD3 genomes

AF:

0.0479

AC:

7281

AN:

152046

Hom.:

253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0466

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.0299

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.0729

Gnomad OTH

AF:

0.0484

GnomAD3 exomes

AF:

0.0521

AC:

13097

AN:

251166

Hom.:

475

AF XY:

0.0551

AC XY:

7483

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0482

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.0708

Gnomad OTH exome

AF:

0.0601

GnomAD4 exome

AF:

0.0661

AC:

96671

AN:

1461702

Hom.:

3555

Cov.:

AF XY:

0.0661

AC XY:

48081

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.0358

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0474

Gnomad4 FIN exome

AF:

0.0324

Gnomad4 NFE exome

AF:

0.0736

Gnomad4 OTH exome

AF:

0.0614

GnomAD4 genome

AF:

0.0478

AC:

7277

AN:

152164

Hom.:

253

Cov.:

AF XY:

0.0453

AC XY:

3368

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.0465

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0419

Gnomad4 FIN

AF:

0.0299

Gnomad4 NFE

AF:

0.0729

Gnomad4 OTH

AF:

0.0479

Alfa

AF:

0.0653

Hom.:

454

Bravo

AF:

0.0479

TwinsUK

AF:

0.0839

AC:

311

ALSPAC

AF:

0.0724

AC:

279

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.0715

AC:

615

ExAC

AF:

0.0517

AC:

6271

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0738

EpiControl

AF:

0.0755

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_addAF

Benign

-0.10

BayesDel_noAF

Pathogenic

0.15

Cadd

Uncertain

Dann

Benign

0.90

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.019

MutationTaster

Benign

1.0

D;D;D;D;D

Vest4

0.14

GERP RS

-11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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