rs569284

chr6-154143195-A-Cchr6-154143195-A-Gchr6-154143195-A-T

Variant summary

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

The ENST00000337049.8(OPRM1):c.1164+51723A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,240 control chromosomes in the GnomAD database, including 741 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 0.091 (741 hom., cov: 32)
• Consequence: OPRM1 ENST00000337049.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_001008503.3	c.1164+51723A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000337049.8	c.1164+51723A>C		intron_variant		1
OPRM1	ENST00000524150.2	c.*250+51723A>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13888 AN: 152122 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0913 AC: 13898 AN: 152240 Hom.: 741 Cov.: 32 AF XY: 0.0943 AC XY: 7020 AN XY: 74452

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0685

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.0567

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0575 Hom.: 324

Bravo AF: 0.0943

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.9
Dann	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs569284; hg19: chr6-154464330;