rs1042753

chr6-154039695-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000914.5(OPRM1):c.151G>A(p.Asp51Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: OPRM1 NM_000914.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054998428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.151G>A	p.Asp51Asn	missense_variant	1/4	ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.151G>A	p.Asp51Asn	missense_variant	1/4	1	NM_000914.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248948 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135130

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461464 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.055	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.21	N;N;.;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.17	T;T;.;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0040, 0.0, 0.0010	.;B;.;B;B;B;B;B;B;B;B;B
Vest4		0.10, 0.15, 0.15, 0.17, 0.18, 0.18, 0.18, 0.12, 0.18
MutPred		0.27		.;.;.;Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);
MVP		0.23
MPC		0.049
ClinPred		0.23	T
GERP RS		4.9
Varity_R		0.077
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs1042753; hg19: chr6-154360830; COSMIC: COSV105067010;