6-154050016-C-T

Variant names:

• chr6-154050016-C-T
• rs534673
• NM_000914.5:c.290+10182C>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+10182C>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 151,962 control chromosomes in the GnomAD database, including 6,222 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 (6222 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39
• Publications: 6 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]

ENSG00000299863 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.290+10182C>T		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.569+10182C>T		intron	N/A	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.569+10182C>T		intron	N/A	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.290+10182C>T		intron	N/A	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000434900.6	TSL:1	c.569+10182C>T		intron	N/A	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.476+10182C>T		intron	N/A	ENSP00000353598.5	L0E130

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40694 AN: 151844 Hom.: 6193 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0460

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.268 AC: 40781 AN: 151962 Hom.: 6222 Cov.: 32 AF XY: 0.263 AC XY: 19498 AN XY: 74244

African (AFR) AF: 0.404 AC: 16725 AN: 41414

American (AMR) AF: 0.297 AC: 4530 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3468

East Asian (EAS) AF: 0.0465 AC: 241 AN: 5186

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4820

European-Finnish (FIN) AF: 0.231 AC: 2438 AN: 10562

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14874 AN: 67946

Other (OTH) AF: 0.265 AC: 559 AN: 2108

Alfa AF: 0.252 Hom.: 650

Bravo AF: 0.281

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.081
DANN	Benign	0.14
PhyloP100		-3.4
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: rs534673; hg19: chr6-154371151;