6-154094299-G-T

Variant names:

• chr6-154094299-G-T
• rs660756
• ENST00000522739.5:n.*45G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000522739.5(OPRM1):​n.*45G>T variant causes a non coding transcript exon 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 ENST00000522739.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 17 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522739.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.1164+2827G>T		intron	N/A	NP_000905.3
	OPRM1	NR_104348.1		n.1388G>T		non_coding_transcript_exon	Exon 4 of 5
	OPRM1	NR_104349.1		n.1388G>T		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000522739.5	TSL:1	n.*45G>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000428018.1
	OPRM1	ENST00000522739.5	TSL:1	n.*45G>T		3_prime_UTR	Exon 4 of 5	ENSP00000428018.1
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.1164+2827G>T		intron	N/A	ENSP00000328264.7

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

GnomAD2 exomes AF: 0.729 AC: 93406 AN: 128178 AF XY: 0.732

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 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

African (AFR) AF: 0.628 AC: 12180 AN: 19408

American (AMR) AF: 0.771 AC: 21556 AN: 27968

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 9882 AN: 14436

East Asian (EAS) AF: 0.884 AC: 10343 AN: 11698

South Asian (SAS) AF: 0.819 AC: 58347 AN: 71268

European-Finnish (FIN) AF: 0.682 AC: 8555 AN: 12552

Middle Eastern (MID) AF: 0.665 AC: 2612 AN: 3926

European-Non Finnish (NFE) AF: 0.654 AC: 452325 AN: 691674

Other (OTH) AF: 0.683 AC: 22676 AN: 33216

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

African (AFR) AF: 0.624 AC: 25913 AN: 41496

American (AMR) AF: 0.730 AC: 11169 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4661 AN: 5192

South Asian (SAS) AF: 0.832 AC: 4017 AN: 4826

European-Finnish (FIN) AF: 0.680 AC: 7202 AN: 10590

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44378 AN: 67986

Other (OTH) AF: 0.705 AC: 1491 AN: 2114

Alfa AF: 0.658 Hom.: 41725

Bravo AF: 0.675

Asia WGS AF: 0.844 AC: 2936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		0.18
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: rs660756; hg19: chr6-154415434;