chr6-154043305-A-G

Variant names:

• chr6-154043305-A-G
• rs634479
• NM_000914.5:c.290+3471A>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+3471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,058 control chromosomes in the GnomAD database, including 2,973 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 (2973 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 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+3471A>G		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.569+3471A>G		intron	N/A	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.569+3471A>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+3471A>G		intron	N/A	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000434900.6	TSL:1	c.569+3471A>G		intron	N/A	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.476+3471A>G		intron	N/A	ENSP00000353598.5	L0E130

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28449 AN: 151940 Hom.: 2964 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.187 AC: 28472 AN: 152058 Hom.: 2973 Cov.: 32 AF XY: 0.184 AC XY: 13685 AN XY: 74338

African (AFR) AF: 0.123 AC: 5112 AN: 41534

American (AMR) AF: 0.268 AC: 4096 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 733 AN: 3464

East Asian (EAS) AF: 0.0466 AC: 242 AN: 5190

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2428 AN: 10566

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14783 AN: 67908

Other (OTH) AF: 0.206 AC: 433 AN: 2106

Alfa AF: 0.213 Hom.: 726

Bravo AF: 0.190

Asia WGS AF: 0.0670 AC: 234 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.65
PhyloP100		0.093
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: rs634479; hg19: chr6-154364440; COSMIC: COSV57684513;