Genetic Variant ENST00000419506.6:c.1231C>G (chr6-154107531-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000419506.6(OPRM1):c.1231C>G(p.Gln411Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 566,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

OPRM1
ENST00000419506.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.685

Publications

27 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12396988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000419506.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OPRM1	NM_000914.5	MANE Select	c.1165-11152C>G		intron	N/A	NP_000905.3
OPRM1	NM_001145286.3		c.1231C>G	p.Gln411Glu	missense	Exon 4 of 4	NP_001138758.1
OPRM1	NM_001145279.4		c.1444-11152C>G		intron	N/A	NP_001138751.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OPRM1	ENST00000419506.6	TSL:1	c.1231C>G	p.Gln411Glu	missense	Exon 4 of 4	ENSP00000403549.2
OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.1165-11152C>G		intron	N/A	ENSP00000328264.7
OPRM1	ENST00000434900.6	TSL:1	c.1444-11152C>G		intron	N/A	ENSP00000394624.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000660

AC:

AN:

151582

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000175

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000177

AC:

AN:

566256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

305480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15812

American (AMR)

AF:

0.00

AC:

AN:

34720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20030

East Asian (EAS)

AF:

0.00

AC:

AN:

32106

South Asian (SAS)

AF:

0.00

AC:

AN:

62776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4078

European-Non Finnish (NFE)

AF:

0.00000315

AC:

AN:

317060

Other (OTH)

AF:

0.00

AC:

AN:

30702

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.81

(source)

DANN

Benign

0.27

Eigen

Benign

-0.77

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.45

M_CAP

Benign

0.0017

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

-0.69

PROVEAN

Benign

-0.060

REVEL

Benign

0.014

Sift

Uncertain

0.021

Vest4

0.14

MutPred

0.25

Gain of disorder (P = 0.0856)

MVP

0.49

ClinPred

0.035

GERP RS

0.23

Mutation Taster

=99/1

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over