rs3778151

Variant names:

• chr6-154072545-T-C
• rs3778151
• NM_000914.5:c.291-17281T>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.291-17281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,164 control chromosomes in the GnomAD database, including 3,181 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 0.19 (3181 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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.291-17281T>C		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.570-17281T>C		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.570-17281T>C		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.291-17281T>C		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.570-17281T>C		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.477-17281T>C		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29194 AN: 152046 Hom.: 3174 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.192 AC: 29235 AN: 152164 Hom.: 3181 Cov.: 32 AF XY: 0.187 AC XY: 13907 AN XY: 74394

African (AFR) AF: 0.287 AC: 11912 AN: 41486

American (AMR) AF: 0.139 AC: 2120 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5188

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4828

European-Finnish (FIN) AF: 0.176 AC: 1862 AN: 10586

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11757 AN: 67996

Other (OTH) AF: 0.179 AC: 378 AN: 2114

Alfa AF: 0.194 Hom.: 861

Bravo AF: 0.193

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		-0.24
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: rs3778151; hg19: chr6-154393680;