chr6-154039507-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000434900.6(OPRM1):c.242C>A(p.Ala81Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,583,090 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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: 𝑓 0.0074 ( 22 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 23 hom. )

Consequence

OPRM1
ENST00000434900.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.177

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024623275).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00738 (1124/152342) while in subpopulation AFR AF = 0.0258 (1073/41580). AF 95% confidence interval is 0.0245. There are 22 homozygotes in GnomAd4. There are 574 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434900.6. 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.-38C>A		5_prime_UTR	Exon 1 of 4	NP_000905.3
OPRM1	NM_001145279.4		c.242C>A	p.Ala81Asp	missense	Exon 3 of 6	NP_001138751.1
OPRM1	NM_001285524.1		c.242C>A	p.Ala81Asp	missense	Exon 2 of 5	NP_001272453.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OPRM1	ENST00000434900.6	TSL:1	c.242C>A	p.Ala81Asp	missense	Exon 3 of 6	ENSP00000394624.2
OPRM1	ENST00000360422.8	TSL:1	c.149C>A	p.Ala50Asp	missense	Exon 1 of 4	ENSP00000353598.5
OPRM1	ENST00000520282.5	TSL:1	c.107C>A	p.Ala36Asp	missense	Exon 2 of 3	ENSP00000430247.1

Frequencies

GnomAD3 genomes

AF:

0.00736

AC:

1121

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00177

AC:

351

AN:

198824

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.00118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000232

Gnomad OTH exome

AF:

0.000591

GnomAD4 exome

AF:

0.000767

AC:

1097

AN:

1430748

Hom.:

Cov.:

AF XY:

0.000655

AC XY:

464

AN XY:

708690

show subpopulations

African (AFR)

AF:

0.0280

AC:

922

AN:

32894

American (AMR)

AF:

0.00144

AC:

AN:

39690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25378

East Asian (EAS)

AF:

0.00

AC:

AN:

38128

South Asian (SAS)

AF:

0.0000487

AC:

AN:

82148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51056

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000638

AC:

AN:

1096508

Other (OTH)

AF:

0.00177

AC:

105

AN:

59218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

141

211

282

352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00738

AC:

1124

AN:

152342

Hom.:

Cov.:

AF XY:

0.00771

AC XY:

574

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0258

AC:

1073

AN:

41580

American (AMR)

AF:

0.00255

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00841

ESP6500AA

AF:

0.0219

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00195

AC:

234

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.8

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00056

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

PhyloP100

-0.18

PROVEAN

Benign

0.17

REVEL

Benign

0.022

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.18

MVP

0.072

MPC

0.068

ClinPred

0.018

GERP RS

-9.3

PromoterAI

-0.0065

Neutral

(source)

gMVP

0.39

Mutation Taster

=298/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over