Genetic Variant OPRD1:p.Cys27Phe (chr1-28812463-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000911.4(OPRD1):c.80G>T(p.Cys27Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 1,522,638 control chromosomes in the GnomAD database, including 588,833 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.90 ( 62309 hom., cov: 35)

Exomes 𝑓: 0.88 ( 526524 hom. )

Consequence

OPRD1
NM_000911.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.260

Publications

86 publications found

Variant links:

Genes affected

OPRD1 (HGNC:8153): (opioid receptor delta 1) Enables G protein-coupled enkephalin receptor activity. Involved in several processes, including G protein-coupled opioid receptor signaling pathway; cellular response to hypoxia; and positive regulation of peptidyl-serine phosphorylation. Is intrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

OPRD1 links:

ENSG00000305996 (HGNC:):

ENSG00000305996 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 (MetaRNN=5.478345E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4 link	c.80G>T	p.Cys27Phe	missense_variant	Exon 1 of 3	ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7 link	c.80G>T	p.Cys27Phe	missense_variant	Exon 1 of 3	1	NM_000911.4	ENSP00000234961.2
ENSG00000305996	ENST00000814652.1 link	n.92-15460G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.903

AC:

137377

AN:

152082

Hom.:

62259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.800

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.942

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.917

Gnomad NFE

AF:

0.864

Gnomad OTH

AF:

0.885

GnomAD2 exomes

AF:

0.910

AC:

109915

AN:

120806

AF XY:

0.909

show subpopulations

Gnomad AFR exome

AF:

0.970

Gnomad AMR exome

AF:

0.940

Gnomad ASJ exome

AF:

0.917

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.877

Gnomad NFE exome

AF:

0.868

Gnomad OTH exome

AF:

0.896

GnomAD4 exome

AF:

0.876

AC:

1200080

AN:

1370444

Hom.:

526524

Cov.:

AF XY:

0.877

AC XY:

593827

AN XY:

676960

show subpopulations

African (AFR)

AF:

0.966

AC:

27704

AN:

28678

American (AMR)

AF:

0.931

AC:

31882

AN:

34234

Ashkenazi Jewish (ASJ)

AF:

0.918

AC:

22390

AN:

24402

East Asian (EAS)

AF:

1.00

AC:

33132

AN:

33142

South Asian (SAS)

AF:

0.939

AC:

72618

AN:

77360

European-Finnish (FIN)

AF:

0.875

AC:

31681

AN:

36200

Middle Eastern (MID)

AF:

0.913

AC:

4434

AN:

4854

European-Non Finnish (NFE)

AF:

0.861

AC:

925356

AN:

1074412

Other (OTH)

AF:

0.890

AC:

50883

AN:

57162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

8348

16697

25045

33394

41742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20786

41572

62358

83144

103930

<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:

0.903

AC:

137480

AN:

152194

Hom.:

62309

Cov.:

AF XY:

0.904

AC XY:

67279

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.961

AC:

39920

AN:

41548

American (AMR)

AF:

0.900

AC:

13766

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.920

AC:

3190

AN:

3468

East Asian (EAS)

AF:

0.999

AC:

5155

AN:

5162

South Asian (SAS)

AF:

0.942

AC:

4553

AN:

4832

European-Finnish (FIN)

AF:

0.880

AC:

9332

AN:

10600

Middle Eastern (MID)

AF:

0.911

AC:

266

AN:

292

European-Non Finnish (NFE)

AF:

0.864

AC:

58699

AN:

67966

Other (OTH)

AF:

0.884

AC:

1869

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

701

1401

2102

2802

3503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.878

Hom.:

87830

Bravo

AF:

0.906

TwinsUK

AF:

0.854

AC:

3168

ALSPAC

AF:

0.865

AC:

3332

ESP6500AA

AF:

0.970

AC:

3689

ESP6500EA

AF:

0.889

AC:

6762

ExAC

AF:

0.878

AC:

88436

Asia WGS

AF:

0.960

AC:

3332

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

5.5e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.69

.;N

PhyloP100

0.26

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.87

.;N

REVEL

Benign

0.10

Sift

Benign

0.71

.;T

Sift4G

Benign

0.71

T;T

Polyphen

0.0

.;B

Vest4

0.032

MPC

1.1

ClinPred

0.00014

GERP RS

2.9

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.053

gMVP

0.38

Mutation Taster

=98/2

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