rs11575856

Variant names:

• chr6-154091185-G-A
• rs11575856
• NM_000914.5:c.877G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145279.4(OPRM1):​c.1156G>A​(p.Val386Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000397 in 1,614,048 control chromosomes in the GnomAD database, including 1 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 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (1 hom.)
• Consequence: OPRM1 NM_001145279.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010830998).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145279.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.877G>A	p.Val293Ile	missense	Exon 3 of 4	NP_000905.3
	OPRM1	NM_001145279.4		c.1156G>A	p.Val386Ile	missense	Exon 5 of 6	NP_001138751.1
	OPRM1	NM_001285524.1		c.1156G>A	p.Val386Ile	missense	Exon 4 of 5	NP_001272453.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.877G>A	p.Val293Ile	missense	Exon 3 of 4	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.1156G>A	p.Val386Ile	missense	Exon 5 of 6	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.1063G>A	p.Val355Ile	missense	Exon 3 of 4	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000996 AC: 249 AN: 250074 AF XY: 0.000945

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00995

Gnomad FIN exome AF: 0.000836

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000379 AC: 554 AN: 1461870 Hom.: 1 Cov.: 32 AF XY: 0.000388 AC XY: 282 AN XY: 727234

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00650 AC: 258 AN: 39700

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86256

European-Finnish (FIN) AF: 0.000580 AC: 31 AN: 53418

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.000153 AC: 170 AN: 1112000

Other (OTH) AF: 0.000563 AC: 34 AN: 60396

GnomAD4 genome AF: 0.000572 AC: 87 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74404

African (AFR) AF: 0.000265 AC: 11 AN: 41498

American (AMR) AF: 0.000196 AC: 3 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5180

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.000755 AC: 8 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000463 Hom.: 0

Bravo AF: 0.000552

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000848 AC: 103

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.89
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.42	N
PhyloP100		2.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.069
Sift	Benign	0.48	T
Sift4G	Benign	0.56	T
Polyphen		0.23	B
Vest4		0.13
MVP		0.085
MPC		0.055
ClinPred		0.0069	T
GERP RS		3.1
Varity_R		0.051
gMVP		0.48
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs11575856; hg19: chr6-154412320; COSMIC: COSV57675231; COSMIC: COSV57675231;