ENST00000337049.8:c.1164+48192T>C

Variant names:

• chr6-154139664-T-C
• rs548339
• ENST00000337049.8:c.1164+48192T>C

Variant summary

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

The ENST00000337049.8(OPRM1):​c.1164+48192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,948 control chromosomes in the GnomAD database, including 33,827 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 0.66 (33827 hom., cov: 30)
• Consequence: OPRM1 ENST00000337049.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.968
• Publications: 5 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000337049.8. 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_001008503.3		c.1164+48192T>C		intron	N/A	NP_001008503.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000337049.8	TSL:1	c.1164+48192T>C		intron	N/A	ENSP00000338381.4
	OPRM1	ENST00000524150.2	TSL:5	n.*250+48192T>C		intron	N/A	ENSP00000430575.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100780 AN: 151830 Hom.: 33820 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.664 AC: 100832 AN: 151948 Hom.: 33827 Cov.: 30 AF XY: 0.671 AC XY: 49820 AN XY: 74246

African (AFR) AF: 0.595 AC: 24641 AN: 41420

American (AMR) AF: 0.728 AC: 11110 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2397 AN: 3462

East Asian (EAS) AF: 0.899 AC: 4639 AN: 5162

South Asian (SAS) AF: 0.831 AC: 4007 AN: 4824

European-Finnish (FIN) AF: 0.702 AC: 7410 AN: 10554

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44389 AN: 67956

Other (OTH) AF: 0.702 AC: 1481 AN: 2110

Alfa AF: 0.669 Hom.: 11541

Bravo AF: 0.664

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.65
PhyloP100		0.97
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: rs548339; hg19: chr6-154460799;