chr6-154059877-G-T

Variant names:

• chr6-154059877-G-T
• rs3778148
• NM_000914.5:c.290+20043G>T

Variant summary

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

The NM_000914.5(OPRM1):​c.290+20043G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,124 control chromosomes in the GnomAD database, including 1,535 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 0.14 (1535 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• 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 = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.290+20043G>T		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.569+20043G>T		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.569+20043G>T		intron	N/A	NP_001272453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.290+20043G>T		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.569+20043G>T		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.476+20043G>T		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20869 AN: 152006 Hom.: 1534 Cov.: 32

Gnomad AFR AF: 0.0986

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.137 AC: 20872 AN: 152124 Hom.: 1535 Cov.: 32 AF XY: 0.134 AC XY: 9952 AN XY: 74368

African (AFR) AF: 0.0985 AC: 4086 AN: 41498

American (AMR) AF: 0.115 AC: 1752 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 404 AN: 3466

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5182

South Asian (SAS) AF: 0.0418 AC: 201 AN: 4812

European-Finnish (FIN) AF: 0.195 AC: 2065 AN: 10578

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11618 AN: 67986

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.153 Hom.: 242

Bravo AF: 0.130

Asia WGS AF: 0.0390 AC: 136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.61
PhyloP100		-0.20
Mutation Taster		=100/0	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: rs3778148; hg19: chr6-154381012;