1-28863246-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000911.4(OPRD1):​c.1082C>A​(p.Thr361Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,534,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T361I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

OPRD1
NM_000911.4 missense

Scores

3
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Publications

1 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14619163).
BS2
High AC in GnomAdExome4 at 64 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPRD1NM_000911.4 linkc.1082C>A p.Thr361Asn missense_variant Exon 3 of 3 ENST00000234961.7 NP_000902.3 P41143

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPRD1ENST00000234961.7 linkc.1082C>A p.Thr361Asn missense_variant Exon 3 of 3 1 NM_000911.4 ENSP00000234961.2 P41143

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.0000573
AC:
8
AN:
139528
AF XY:
0.0000384
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000316
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000159
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000463
AC:
64
AN:
1381768
Hom.:
0
Cov.:
32
AF XY:
0.0000351
AC XY:
24
AN XY:
683164
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31108
American (AMR)
AF:
0.000267
AC:
9
AN:
33736
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23286
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36668
South Asian (SAS)
AF:
0.00
AC:
0
AN:
76922
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34708
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5514
European-Non Finnish (NFE)
AF:
0.0000453
AC:
49
AN:
1082350
Other (OTH)
AF:
0.000104
AC:
6
AN:
57476
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.510
Heterozygous variant carriers
0
6
12
17
23
29
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000263
AC:
4
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41470
American (AMR)
AF:
0.000131
AC:
2
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10632
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68038
Other (OTH)
AF:
0.000478
AC:
1
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.000128
ExAC
AF:
0.0000445
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 04, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1082C>A (p.T361N) alteration is located in exon 3 (coding exon 3) of the OPRD1 gene. This alteration results from a C to A substitution at nucleotide position 1082, causing the threonine (T) at amino acid position 361 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.10
.;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.13
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.70
T;T
M_CAP
Pathogenic
0.64
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.0
.;L
PhyloP100
1.6
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.12
.;N
REVEL
Benign
0.075
Sift
Benign
0.081
.;T
Sift4G
Benign
0.50
T;T
Polyphen
0.42
.;B
Vest4
0.26
MVP
0.83
MPC
0.86
ClinPred
0.054
T
GERP RS
3.6
Varity_R
0.11
gMVP
0.34
Mutation Taster
=65/35
polymorphism

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

Other links and lift over

dbSNP: rs751125712; hg19: chr1-29189758; API