rs12216066

Positions:

• chr6-154020423-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
OPRM1	NM_001145279.4	c.-1+9405A>G		intron_variant
OPRM1	NM_001145280.4	c.-11+9405A>G		intron_variant
OPRM1	NM_001145281.3	c.47+9864A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000434900.6	c.-1+9405A>G		intron_variant		1
OPRM1	ENST00000518759.5	c.47+9864A>G		intron_variant		1
OPRM1	ENST00000520282.5	c.10+9405A>G		intron_variant		1
OPRM1	ENST00000520708.5	c.-11+9405A>G		intron_variant		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

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0440

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0477 Hom.: 389

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12216066; hg19: chr6-154341558;