6-154121116-G-C

Variant names:

• chr6-154121116-G-C
• rs644261
• NM_000914.5:c.*2395G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000914.5(OPRM1):​c.*2395G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,086 control chromosomes in the GnomAD database, including 3,189 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.

• Frequency: Genomes: 𝑓 0.20 (3189 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.*2395G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.*2395G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_000914.5	ENSP00000328264.7
OPRM1	ENST00000337049.8	c.1164+29644G>C		intron_variant	Intron 3 of 3	1		ENSP00000338381.4
OPRM1	ENST00000524150.2	n.*250+29644G>C		intron_variant	Intron 2 of 2	5		ENSP00000430575.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29634 AN: 151968 Hom.: 3187 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29660 AN: 152086 Hom.: 3189 Cov.: 32 AF XY: 0.190 AC XY: 14139 AN XY: 74346

African (AFR) AF: 0.129 AC: 5338 AN: 41512

American (AMR) AF: 0.186 AC: 2845 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.0842 AC: 437 AN: 5188

South Asian (SAS) AF: 0.145 AC: 699 AN: 4814

European-Finnish (FIN) AF: 0.188 AC: 1984 AN: 10568

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17000 AN: 67940

Other (OTH) AF: 0.182 AC: 384 AN: 2108

Alfa AF: 0.122 Hom.: 223

Bravo AF: 0.191

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs644261; hg19: chr6-154442251;