6-154054390-A-G

Variant names:

• chr6-154054390-A-G
• rs520321
• NM_000914.5:c.290+14556A>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.290+14556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 137,710 control chromosomes in the GnomAD database, including 367 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 0.074 (367 hom., cov: 27)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 3 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]

ENSG00000299863 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.115 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.290+14556A>G		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.569+14556A>G		intron	N/A	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.569+14556A>G		intron	N/A	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.290+14556A>G		intron	N/A	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000434900.6	TSL:1	c.569+14556A>G		intron	N/A	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.476+14556A>G		intron	N/A	ENSP00000353598.5	L0E130

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 10168 AN: 137636 Hom.: 365 Cov.: 27

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0659

Gnomad EAS AF: 0.000783

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0699

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0739 AC: 10170 AN: 137710 Hom.: 367 Cov.: 27 AF XY: 0.0703 AC XY: 4697 AN XY: 66812

African (AFR) AF: 0.0662 AC: 2546 AN: 38444

American (AMR) AF: 0.120 AC: 1512 AN: 12598

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 209 AN: 3172

East Asian (EAS) AF: 0.000785 AC: 4 AN: 5098

South Asian (SAS) AF: 0.0341 AC: 159 AN: 4660

European-Finnish (FIN) AF: 0.0524 AC: 425 AN: 8116

Middle Eastern (MID) AF: 0.0675 AC: 17 AN: 252

European-Non Finnish (NFE) AF: 0.0806 AC: 5055 AN: 62694

Other (OTH) AF: 0.0861 AC: 161 AN: 1870

Alfa AF: 0.0887 Hom.: 163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.48
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: rs520321; hg19: chr6-154375525;