rs3778150

Variant names:

• chr6-154062523-T-C
• rs3778150
• NM_000914.5:c.290+22689T>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.290+22689T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,930 control chromosomes in the GnomAD database, including 2,142 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 0.16 (2142 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 27 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+22689T>C		intron_variant	Intron 1 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.290+22689T>C		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24774 AN: 151812 Hom.: 2142 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0452

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.163 AC: 24779 AN: 151930 Hom.: 2142 Cov.: 32 AF XY: 0.159 AC XY: 11772 AN XY: 74234

African (AFR) AF: 0.186 AC: 7694 AN: 41464

American (AMR) AF: 0.123 AC: 1883 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3466

East Asian (EAS) AF: 0.0457 AC: 236 AN: 5168

South Asian (SAS) AF: 0.0458 AC: 221 AN: 4824

European-Finnish (FIN) AF: 0.196 AC: 2070 AN: 10564

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11682 AN: 67880

Other (OTH) AF: 0.146 AC: 308 AN: 2106

Alfa AF: 0.164 Hom.: 1398

Bravo AF: 0.159

Asia WGS AF: 0.0460 AC: 160 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.69
PhyloP100		1.3
Mutation Taster		=94/6	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: rs3778150; hg19: chr6-154383658;