6-154047412-C-T

Variant names:

• chr6-154047412-C-T
• rs511435
• NM_000914.5:c.290+7578C>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+7578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,858 control chromosomes in the GnomAD database, including 3,413 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 0.21 (3413 hom., cov: 30)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 14 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.266 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+7578C>T		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.569+7578C>T		intron	N/A	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.569+7578C>T		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+7578C>T		intron	N/A	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000434900.6	TSL:1	c.569+7578C>T		intron	N/A	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.476+7578C>T		intron	N/A	ENSP00000353598.5	L0E130

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31129 AN: 151740 Hom.: 3404 Cov.: 30

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.205 AC: 31154 AN: 151858 Hom.: 3413 Cov.: 30 AF XY: 0.201 AC XY: 14934 AN XY: 74228

African (AFR) AF: 0.187 AC: 7744 AN: 41360

American (AMR) AF: 0.273 AC: 4161 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3462

East Asian (EAS) AF: 0.0466 AC: 241 AN: 5174

South Asian (SAS) AF: 0.0719 AC: 346 AN: 4810

European-Finnish (FIN) AF: 0.230 AC: 2422 AN: 10542

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14741 AN: 67950

Other (OTH) AF: 0.220 AC: 462 AN: 2102

Alfa AF: 0.220 Hom.: 1675

Bravo AF: 0.211

Asia WGS AF: 0.0710 AC: 248 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	0.38
DANN	Benign	0.55
PhyloP100		-0.73
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: rs511435; hg19: chr6-154368547;