rs12216066

Variant names:

• chr6-154020423-A-G
• rs12216066
• ENST00000434900.6:c.-1+9405A>G

Variant summary

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

The ENST00000434900.6(OPRM1):​c.-1+9405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,264 control chromosomes in the GnomAD database, including 1,070 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 0.089 (1070 hom., cov: 32)
• Consequence: OPRM1 ENST00000434900.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_001145279.4	c.-1+9405A>G		intron_variant	Intron 1 of 5		NP_001138751.1
OPRM1	NM_001145281.3	c.47+9864A>G		intron_variant	Intron 1 of 3		NP_001138753.1
OPRM1	NM_001145280.4	c.-11+9405A>G		intron_variant	Intron 1 of 3		NP_001138752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000434900.6	c.-1+9405A>G		intron_variant	Intron 1 of 5	1		ENSP00000394624.2
OPRM1	ENST00000518759.5	c.47+9864A>G		intron_variant	Intron 1 of 3	1		ENSP00000430260.1
OPRM1	ENST00000520708.5	c.-11+9405A>G		intron_variant	Intron 1 of 3	1		ENSP00000430876.1
OPRM1	ENST00000520282.5	c.10+9405A>G		intron_variant	Intron 1 of 2	1		ENSP00000430247.1

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13501 AN: 152148 Hom.: 1066 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.0746

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0440

Gnomad OTH AF: 0.0606

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

GnomAD4 genome AF: 0.0888 AC: 13523 AN: 152264 Hom.: 1070 Cov.: 32 AF XY: 0.0875 AC XY: 6512 AN XY: 74450

African (AFR) AF: 0.208 AC: 8632 AN: 41524

American (AMR) AF: 0.0346 AC: 530 AN: 15298

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

East Asian (EAS) AF: 0.0906 AC: 470 AN: 5188

South Asian (SAS) AF: 0.0738 AC: 356 AN: 4824

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10618

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0440 AC: 2994 AN: 68020

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0580 Hom.: 1458

Bravo AF: 0.0945

Asia WGS AF: 0.0890 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.60
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12216066; hg19: chr6-154341558;