rs553202

Variant names:

• chr6-154043682-C-T
• rs553202
• NM_000914.5:c.290+3848C>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.290+3848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,804 control chromosomes in the GnomAD database, including 6,197 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 0.27 (6197 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 11 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+3848C>T		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+3848C>T		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40648 AN: 151684 Hom.: 6171 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0463

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.195

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.268 AC: 40729 AN: 151804 Hom.: 6197 Cov.: 32 AF XY: 0.262 AC XY: 19464 AN XY: 74192

African (AFR) AF: 0.402 AC: 16650 AN: 41422

American (AMR) AF: 0.298 AC: 4551 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3468

East Asian (EAS) AF: 0.0468 AC: 242 AN: 5176

South Asian (SAS) AF: 0.0719 AC: 347 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2423 AN: 10536

Middle Eastern (MID) AF: 0.192 AC: 55 AN: 286

European-Non Finnish (NFE) AF: 0.220 AC: 14888 AN: 67802

Other (OTH) AF: 0.267 AC: 564 AN: 2112

Alfa AF: 0.262 Hom.: 702

Bravo AF: 0.281

Asia WGS AF: 0.0870 AC: 301 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.12
PhyloP100		-0.23
Mutation Taster		=96/4	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: rs553202; hg19: chr6-154364817;