rs557748

Variant names:

• chr6-154043167-G-A
• rs557748
• NM_000914.5:c.290+3333G>A

Variant summary

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

The NM_000914.5(OPRM1):​c.290+3333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,056 control chromosomes in the GnomAD database, including 3,020 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 0.19 (3020 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+3333G>A		intron_variant	Intron 1 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.290+3333G>A		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28788 AN: 151938 Hom.: 3010 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.189 AC: 28812 AN: 152056 Hom.: 3020 Cov.: 32 AF XY: 0.186 AC XY: 13858 AN XY: 74318

African (AFR) AF: 0.133 AC: 5540 AN: 41520

American (AMR) AF: 0.268 AC: 4089 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3468

East Asian (EAS) AF: 0.0463 AC: 240 AN: 5186

South Asian (SAS) AF: 0.0707 AC: 341 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2434 AN: 10556

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14695 AN: 67920

Other (OTH) AF: 0.206 AC: 435 AN: 2108

Alfa AF: 0.216 Hom.: 615

Bravo AF: 0.192

Asia WGS AF: 0.0680 AC: 235 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.58
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs557748; hg19: chr6-154364302;