NM_000914.5:c.291-24597A>C

Variant names:

• chr6-154065229-A-C
• rs12333298
• NM_000914.5:c.291-24597A>C

Variant summary

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

The NM_000914.5(OPRM1):​c.291-24597A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 150,232 control chromosomes in the GnomAD database, including 1,502 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 0.14 (1502 hom., cov: 30)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.291-24597A>C		intron_variant	Intron 1 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.291-24597A>C		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20547 AN: 150130 Hom.: 1501 Cov.: 30

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0460

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.137 AC: 20548 AN: 150232 Hom.: 1502 Cov.: 30 AF XY: 0.133 AC XY: 9769 AN XY: 73272

African (AFR) AF: 0.0983 AC: 4010 AN: 40778

American (AMR) AF: 0.113 AC: 1709 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 400 AN: 3458

East Asian (EAS) AF: 0.0465 AC: 238 AN: 5114

South Asian (SAS) AF: 0.0418 AC: 198 AN: 4738

European-Finnish (FIN) AF: 0.193 AC: 1959 AN: 10144

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.170 AC: 11536 AN: 67662

Other (OTH) AF: 0.122 AC: 253 AN: 2078

Alfa AF: 0.152 Hom.: 244

Bravo AF: 0.130

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.72
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: rs12333298; hg19: chr6-154386364;