Genetic Variant NM_000914.5:c.290+79C>T (chr6-154039913-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

-12

BP4_StrongBA1

The NM_000914.5(OPRM1):c.290+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 1,313,184 control chromosomes in the GnomAD database, including 1,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 120 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1491 hom. )

Consequence

OPRM1
NM_000914.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.684

Publications

10 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5 link	c.290+79C>T		intron_variant	Intron 1 of 3	ENST00000330432.12	NP_000905.3	P35372-1G8XRH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 link	c.290+79C>T		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7		P35372-1

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4725

AN:

152052

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00841

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.0953

Gnomad SAS

AF:

0.0559

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0436

Gnomad OTH

AF:

0.0240

GnomAD4 exome

AF:

0.0460

AC:

53429

AN:

1161014

Hom.:

1491

AF XY:

0.0466

AC XY:

26651

AN XY:

571486

show subpopulations

African (AFR)

AF:

0.00540

AC:

145

AN:

26860

American (AMR)

AF:

0.0113

AC:

291

AN:

25848

Ashkenazi Jewish (ASJ)

AF:

0.00896

AC:

164

AN:

18296

East Asian (EAS)

AF:

0.0938

AC:

3485

AN:

37160

South Asian (SAS)

AF:

0.0525

AC:

3261

AN:

62092

European-Finnish (FIN)

AF:

0.0320

AC:

1090

AN:

34012

Middle Eastern (MID)

AF:

0.0134

AC:

AN:

4262

European-Non Finnish (NFE)

AF:

0.0475

AC:

42908

AN:

902850

Other (OTH)

AF:

0.0409

AC:

2028

AN:

49634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2517

5034

7551

10068

12585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1678

3356

5034

6712

8390

<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:

0.0310

AC:

4717

AN:

152170

Hom.:

120

Cov.:

AF XY:

0.0306

AC XY:

2275

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00838

AC:

348

AN:

41512

American (AMR)

AF:

0.0121

AC:

185

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3472

East Asian (EAS)

AF:

0.0947

AC:

490

AN:

5172

South Asian (SAS)

AF:

0.0551

AC:

265

AN:

4810

European-Finnish (FIN)

AF:

0.0298

AC:

316

AN:

10600

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0436

AC:

2967

AN:

67996

Other (OTH)

AF:

0.0242

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

238

475

713

950

1188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0332

Hom.:

Bravo

AF:

0.0286

Asia WGS

AF:

0.0670

AC:

234

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.0

(source)

DANN

Benign

0.81

PhyloP100

0.68

PromoterAI

0.0025

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over