6-154092539-C-T

Variant names:

• chr6-154092539-C-T
• rs533586
• NM_000914.5:c.1164+1067C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000914.5(OPRM1):​c.1164+1067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,018 control chromosomes in the GnomAD database, including 34,460 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 (34460 hom., cov: 31)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 12 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 -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 rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+1067C>T		intron_variant	Intron 3 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1164+1067C>T		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101854 AN: 151900 Hom.: 34455 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.670 AC: 101893 AN: 152018 Hom.: 34460 Cov.: 31 AF XY: 0.677 AC XY: 50336 AN XY: 74328

African (AFR) AF: 0.625 AC: 25905 AN: 41448

American (AMR) AF: 0.729 AC: 11145 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2388 AN: 3468

East Asian (EAS) AF: 0.898 AC: 4641 AN: 5166

South Asian (SAS) AF: 0.835 AC: 4026 AN: 4820

European-Finnish (FIN) AF: 0.681 AC: 7179 AN: 10546

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.653 AC: 44363 AN: 67972

Other (OTH) AF: 0.705 AC: 1488 AN: 2110

Alfa AF: 0.664 Hom.: 21252

Bravo AF: 0.675

Asia WGS AF: 0.846 AC: 2941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		-0.32
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: rs533586; hg19: chr6-154413674;