rs12214130

chr6-154019482-A-Gchr6-154019482-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000434900.6(OPRM1):c.-1+8464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 152,100 control chromosomes in the GnomAD database, including 467 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 0.066 (467 hom., cov: 31)
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_001145279.4	c.-1+8464A>G		intron_variant
OPRM1	NM_001145280.4	c.-11+8464A>G		intron_variant
OPRM1	NM_001145281.3	c.47+8923A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000434900.6	c.-1+8464A>G		intron_variant		1
OPRM1	ENST00000518759.5	c.47+8923A>G		intron_variant		1
OPRM1	ENST00000520282.5	c.10+8464A>G		intron_variant		1
OPRM1	ENST00000520708.5	c.-11+8464A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9964 AN: 151982 Hom.: 462 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.0746

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0506

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

GnomAD4 genome AF: 0.0656 AC: 9979 AN: 152100 Hom.: 467 Cov.: 31 AF XY: 0.0652 AC XY: 4846 AN XY: 74360

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.0898

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0373 Hom.: 82

Bravo AF: 0.0687

Asia WGS AF: 0.0840 AC: 293 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	2.8
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12214130; hg19: chr6-154340617;