6-154094299-G-T

Position:

• chr6-154094299-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000330432.12(OPRM1):​c.1164+2827G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,038,312 control chromosomes in the GnomAD database, including 238,747 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 0.67 (34495 hom., cov: 32)
  • Exomes 𝑓: 0.68 (204252 hom.)
• Consequence: OPRM1 ENST00000330432.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+2827G>T		intron_variant		ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1164+2827G>T		intron_variant		1	NM_000914.5	ENSP00000328264	P1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101935 AN: 152048 Hom.: 34491 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.707

GnomAD3 exomes AF: 0.729 AC: 93406 AN: 128178 Hom.: 34510 AF XY: 0.732 AC XY: 51359 AN XY: 70194

Gnomad AFR exome AF: 0.630

Gnomad AMR exome AF: 0.770

Gnomad ASJ exome AF: 0.684

Gnomad EAS exome AF: 0.881

Gnomad SAS exome AF: 0.822

Gnomad FIN exome AF: 0.691

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.710

GnomAD4 exome AF: 0.675 AC: 598476 AN: 886146 Hom.: 204252 Cov.: 12 AF XY: 0.681 AC XY: 303662 AN XY: 445850

Gnomad4 AFR exome AF: 0.628

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.685

Gnomad4 EAS exome AF: 0.884

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.670 AC: 101973 AN: 152166 Hom.: 34495 Cov.: 32 AF XY: 0.677 AC XY: 50362 AN XY: 74380

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.705

Alfa AF: 0.657 Hom.: 29645

Bravo AF: 0.675

Asia WGS AF: 0.844 AC: 2936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs660756; hg19: chr6-154415434;