Variant 6-154107531-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBA1

The ENST00000419506.6(OPRM1):c.1231C>T(p.Gln411Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 718,426 control chromosomes in the GnomAD database, including 17,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3490 hom., cov: 32)

Exomes 𝑓: 0.22 ( 14070 hom. )

Consequence

OPRM1
ENST00000419506.6 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.685

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Stoplost variant in ENST00000419506.6 Downstream stopcodon found after 436 codons.

BP6

Variant 6-154107531-C-T is Benign according to our data. Variant chr6-154107531-C-T is described in ClinVar as [Benign]. Clinvar id is 403268.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.1165-11152C>T		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.1165-11152C>T		intron_variant		1	NM_000914.5	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31411

AN:

152066

Hom.:

3487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0846

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.195

AC:

29485

AN:

151582

Hom.:

3161

AF XY:

0.196

AC XY:

15800

AN XY:

80618

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.0964

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.216

AC:

122057

AN:

566240

Hom.:

14070

Cov.:

AF XY:

0.215

AC XY:

65748

AN XY:

305474

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.0860

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.207

AC:

31444

AN:

152186

Hom.:

3490

Cov.:

AF XY:

0.201

AC XY:

14973

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.0846

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.193

Alfa

AF:

0.227

Hom.:

5490

Bravo

AF:

0.204

TwinsUK

AF:

0.262

AC:

971

ALSPAC

AF:

0.249

AC:

958

ExAC

AF:

0.179

AC:

3917

Asia WGS

AF:

0.122

AC:

423

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 360/2178=16.5% -

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

-0.90

BayesDel_noAF

Benign

-0.92

Cadd

Benign

2.0

Dann

Benign

0.80

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0017

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P;P;P

Vest4

0.086

GERP RS

0.23

Splicing

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