6-154119607-A-G

Position:

• chr6-154119607-A-G

Variant summary

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

The NM_000914.5(OPRM1):​c.*886A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 198,566 control chromosomes in the GnomAD database, including 44,032 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 (34325 hom., cov: 33)
  • Exomes 𝑓: 0.63 (9707 hom.)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.*886A>G		3_prime_UTR_variant	4/4	ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.*886A>G		3_prime_UTR_variant	4/4	1	NM_000914.5	P1
OPRM1	ENST00000337049.8	c.1164+28135A>G		intron_variant		1
OPRM1	ENST00000524150.2	c.*250+28135A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101646 AN: 151986 Hom.: 34327 Cov.: 33

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.627 AC: 29124 AN: 46462 Hom.: 9707 AF XY: 0.626 AC XY: 14250 AN XY: 22770

Gnomad4 AFR exome AF: 0.578

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.859

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.668 AC: 101679 AN: 152104 Hom.: 34325 Cov.: 33 AF XY: 0.675 AC XY: 50204 AN XY: 74358

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.704

Alfa AF: 0.659 Hom.: 28893

Bravo AF: 0.672

Asia WGS AF: 0.843 AC: 2930 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs671531; hg19: chr6-154440742;