rs1799971

chr6-154039662-A-G

• Frequency:
  • Genomes: 𝑓 0.13 (1912 hom., cov: 32)
  • Exomes 𝑓: 0.19 (5913 hom.)
• Consequence: OPRM1 NM_000914 missense
• Clinical Significance: Uncertain significance; drug response no assertion criteria provided U:1 O:1
• Conservation: PhyloP100: 4.31

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity OPRM_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.002016455).
• BA1: GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.118A>G	p.Asn40Asp	missense_variant	1/4	ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.118A>G	p.Asn40Asp	missense_variant	1/4	1	NM_000914.5	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19734 AN: 152054 Hom.: 1912 Cov.: 32

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.139

GnomAD3 exomes AF: 0.188 AC: 46959 AN: 249224 Hom.: 5913 AF XY: 0.196 AC XY: 26451 AN XY: 135238

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.372

Gnomad SAS exome AF: 0.363

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.153 AC: 223836 AN: 1461520 Hom.: 21864 AF XY: 0.159 AC XY: 115536 AN XY: 726998

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.163

Alfa AF: 0.139 Hom.: 4404

Bravo AF: 0.120

TwinsUK AF: 0.129 AC: 479

ALSPAC AF: 0.127 AC: 489

ESP6500AA AF: 0.0306 AC: 122

ESP6500EA AF: 0.129 AC: 1070

ExAC AF: 0.185 AC: 22379

Asia WGS AF: 0.377 AC: 1311 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.136

ClinVar

Significance: Uncertain significance; drug response

Submissions summary: Uncertain:1Other:1

Revision: no assertion criteria provided

LINK:

Submissions by phenotype

Opioid dependence, susceptibility to, 1 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jun 30, 2009

- -

Tramadol response Other:1

drug response, no assertion criteria provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.57

T

BayesDel_noAF

Benign

-0.44

Cadd

Uncertain

24

Dann

Uncertain

1.0

Eigen

Benign

-0.011

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.027

N

LIST_S2

Benign

0.69

T;T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

T

MutationTaster

Benign

0.0030

P;P;P;P;P;P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.62

T

PROVEAN

Benign

-2.1

N;N;.;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.024

D;D;.;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;T;D;D;D;T;D;D;D

Polyphen

0.081, 0.23, 0.0070, 0.73, 0.49, 0.95, 0.0010, 0.22, 0.0030

.;B;.;B;B;P;P;P;B;P;B;B

Vest4

0.18, 0.097, 0.17, 0.18, 0.19, 0.19, 0.20, 0.22, 0.19, 0.19

MPC

0.11

ClinPred

0.028

T

GERP RS

5.8

Varity_R

0.17

gMVP

0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799971; hg19: chr6-154360797; COSMIC: COSV57673061;