chr6-154246729-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000337049.8(OPRM1):​c.1201C>T​(p.Arg401Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,613,866 control chromosomes in the GnomAD database, including 3,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.048 ( 253 hom., cov: 31)
Exomes 𝑓: 0.066 ( 3555 hom. )

Consequence

OPRM1
ENST00000337049.8 stop_gained

Scores

1
6

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -5.05
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]
IPCEF1 (HGNC:21204): (interaction protein for cytohesin exchange factors 1) Predicted to enable peroxidase activity. Predicted to be involved in response to oxidative stress. Predicted to be located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IPCEF1NM_001130700.2 linkuse as main transcriptc.108G>A p.Ser36= synonymous_variant 5/12 ENST00000367220.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IPCEF1ENST00000367220.9 linkuse as main transcriptc.108G>A p.Ser36= synonymous_variant 5/122 NM_001130700.2 A2Q8WWN9-2

Frequencies

GnomAD3 genomes
AF:
0.0479
AC:
7281
AN:
152046
Hom.:
253
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0130
Gnomad AMI
AF:
0.0363
Gnomad AMR
AF:
0.0466
Gnomad ASJ
AF:
0.115
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0423
Gnomad FIN
AF:
0.0299
Gnomad MID
AF:
0.0541
Gnomad NFE
AF:
0.0729
Gnomad OTH
AF:
0.0484
GnomAD3 exomes
AF:
0.0521
AC:
13097
AN:
251166
Hom.:
475
AF XY:
0.0551
AC XY:
7483
AN XY:
135750
show subpopulations
Gnomad AFR exome
AF:
0.0124
Gnomad AMR exome
AF:
0.0359
Gnomad ASJ exome
AF:
0.112
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0482
Gnomad FIN exome
AF:
0.0294
Gnomad NFE exome
AF:
0.0708
Gnomad OTH exome
AF:
0.0601
GnomAD4 exome
AF:
0.0661
AC:
96671
AN:
1461702
Hom.:
3555
Cov.:
32
AF XY:
0.0661
AC XY:
48081
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.0109
Gnomad4 AMR exome
AF:
0.0358
Gnomad4 ASJ exome
AF:
0.113
Gnomad4 EAS exome
AF:
0.000252
Gnomad4 SAS exome
AF:
0.0474
Gnomad4 FIN exome
AF:
0.0324
Gnomad4 NFE exome
AF:
0.0736
Gnomad4 OTH exome
AF:
0.0614
GnomAD4 genome
AF:
0.0478
AC:
7277
AN:
152164
Hom.:
253
Cov.:
31
AF XY:
0.0453
AC XY:
3368
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0130
Gnomad4 AMR
AF:
0.0465
Gnomad4 ASJ
AF:
0.115
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0419
Gnomad4 FIN
AF:
0.0299
Gnomad4 NFE
AF:
0.0729
Gnomad4 OTH
AF:
0.0479
Alfa
AF:
0.0653
Hom.:
454
Bravo
AF:
0.0479
TwinsUK
AF:
0.0839
AC:
311
ALSPAC
AF:
0.0724
AC:
279
ESP6500AA
AF:
0.0166
AC:
73
ESP6500EA
AF:
0.0715
AC:
615
ExAC
AF:
0.0517
AC:
6271
Asia WGS
AF:
0.0150
AC:
53
AN:
3478
EpiCase
AF:
0.0738
EpiControl
AF:
0.0755

ClinVar

Significance: drug response
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Tramadol response Other:1
drug response, no assertion criteria providedresearchBruce Budowle Laboratory, University of North Texas Health Science CenterApr 28, 2018- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Pathogenic
0.15
CADD
Uncertain
25
DANN
Benign
0.90
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.019
N
MutationTaster
Benign
1.0
D;D;D;D;D
Vest4
0.14
GERP RS
-11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34427887; hg19: chr6-154567863; COSMIC: COSV54552179; API