rs17174638

Variant names:

• chr6-154039434-C-T
• rs17174638
• ENST00000434900.6:c.169C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001145279.4(OPRM1):​c.169C>T​(p.Gln57*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,551,464 control chromosomes in the GnomAD database, including 425 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q57Q) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.030 (211 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (214 hom.)
• Consequence: OPRM1 NM_001145279.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 16 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

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.-111C>T		5_prime_UTR	Exon 1 of 4	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.169C>T	p.Gln57*	stop_gained	Exon 3 of 6	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.169C>T	p.Gln57*	stop_gained	Exon 2 of 5	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.169C>T	p.Gln57*	stop_gained	Exon 3 of 6	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.76C>T	p.Gln26*	stop_gained	Exon 1 of 4	ENSP00000353598.5	L0E130
	OPRM1	ENST00000520282.5	TSL:1	c.34C>T	p.Gln12*	stop_gained	Exon 2 of 3	ENSP00000430247.1	E7EW71

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4512 AN: 152110 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00627 AC: 978 AN: 155892 AF XY: 0.00463

Gnomad AFR exome AF: 0.0996

Gnomad AMR exome AF: 0.00530

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000183

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000380

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00314 AC: 4398 AN: 1399236 Hom.: 214 Cov.: 31 AF XY: 0.00276 AC XY: 1908 AN XY: 690116

African (AFR) AF: 0.103 AC: 3257 AN: 31592

American (AMR) AF: 0.00689 AC: 246 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.0000840 AC: 3 AN: 35734

South Asian (SAS) AF: 0.000581 AC: 46 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49274

Middle Eastern (MID) AF: 0.0116 AC: 66 AN: 5696

European-Non Finnish (NFE) AF: 0.000281 AC: 303 AN: 1078852

Other (OTH) AF: 0.00822 AC: 477 AN: 58014

GnomAD4 genome AF: 0.0298 AC: 4531 AN: 152228 Hom.: 211 Cov.: 32 AF XY: 0.0286 AC XY: 2132 AN XY: 74452

African (AFR) AF: 0.103 AC: 4282 AN: 41530

American (AMR) AF: 0.0114 AC: 175 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68008

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.0144 Hom.: 162

Bravo AF: 0.0334

ESP6500AA AF: 0.102 AC: 141

ESP6500EA AF: 0.000314 AC: 1

ExAC AF: 0.00386 AC: 342

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	0.050
CADD	Benign	0.0090
DANN	Uncertain	0.99
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.00022	N
PhyloP100		-1.6
Vest4		0.59
GERP RS		-3.4
PromoterAI		-0.038	Neutral
Mutation Taster		=153/47	polymorphism (auto)

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: rs17174638; hg19: chr6-154360569;