6-154116117-A-G

Variant names:

• chr6-154116117-A-G
• rs632395
• NM_000914.5:c.1165-2566A>G

Variant summary

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

The NM_000914.5(OPRM1):​c.1165-2566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,102 control chromosomes in the GnomAD database, including 60,058 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 0.89 (60058 hom., cov: 30)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 7 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 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.1165-2566A>G		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.1444-2566A>G		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.1444-2566A>G		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.1165-2566A>G		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.1444-2566A>G		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000337049.8	TSL:1	c.1164+24645A>G		intron	N/A	ENSP00000338381.4

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134910 AN: 151984 Hom.: 60038 Cov.: 30

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.887 AC: 134985 AN: 152102 Hom.: 60058 Cov.: 30 AF XY: 0.888 AC XY: 66025 AN XY: 74326

African (AFR) AF: 0.826 AC: 34253 AN: 41472

American (AMR) AF: 0.924 AC: 14126 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3072 AN: 3468

East Asian (EAS) AF: 0.983 AC: 5075 AN: 5164

South Asian (SAS) AF: 0.974 AC: 4673 AN: 4800

European-Finnish (FIN) AF: 0.876 AC: 9275 AN: 10582

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61545 AN: 68018

Other (OTH) AF: 0.901 AC: 1899 AN: 2108

Alfa AF: 0.903 Hom.: 104413

Bravo AF: 0.889

Asia WGS AF: 0.968 AC: 3368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.43
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: rs632395; hg19: chr6-154437252;