6-154072696-A-G

Variant names:

• chr6-154072696-A-G
• rs3778152
• NM_000914.5:c.291-17130A>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.291-17130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,328 control chromosomes in the GnomAD database, including 189 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 0.047 (189 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0864 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.291-17130A>G		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.570-17130A>G		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.570-17130A>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.291-17130A>G		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.570-17130A>G		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.477-17130A>G		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7157 AN: 152210 Hom.: 188 Cov.: 33

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0334

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

GnomAD4 genome AF: 0.0470 AC: 7160 AN: 152328 Hom.: 189 Cov.: 33 AF XY: 0.0463 AC XY: 3447 AN XY: 74488

African (AFR) AF: 0.0666 AC: 2767 AN: 41574

American (AMR) AF: 0.0203 AC: 311 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.0933 AC: 484 AN: 5188

South Asian (SAS) AF: 0.0630 AC: 304 AN: 4826

European-Finnish (FIN) AF: 0.0298 AC: 317 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0413 AC: 2809 AN: 68028

Other (OTH) AF: 0.0336 AC: 71 AN: 2116

Alfa AF: 0.0445 Hom.: 28

Bravo AF: 0.0475

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.80
DANN	Benign	0.63
PhyloP100		-0.51
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: rs3778152; hg19: chr6-154393831;