NM_000914.5:c.290+3170C>T

Variant names:

• chr6-154043004-C-T
• rs3798676
• NM_000914.5:c.290+3170C>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+3170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 152,188 control chromosomes in the GnomAD database, including 118 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 0.031 (118 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0858 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+3170C>T		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.569+3170C>T		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.569+3170C>T		intron	N/A	NP_001272453.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.290+3170C>T		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.569+3170C>T		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.476+3170C>T		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4738 AN: 152070 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.00865

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0311 AC: 4735 AN: 152188 Hom.: 118 Cov.: 32 AF XY: 0.0307 AC XY: 2286 AN XY: 74410

African (AFR) AF: 0.00874 AC: 363 AN: 41532

American (AMR) AF: 0.0121 AC: 185 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3468

East Asian (EAS) AF: 0.0927 AC: 480 AN: 5180

South Asian (SAS) AF: 0.0557 AC: 269 AN: 4826

European-Finnish (FIN) AF: 0.0300 AC: 318 AN: 10594

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0437 AC: 2974 AN: 67984

Other (OTH) AF: 0.0241 AC: 51 AN: 2112

Alfa AF: 0.0339 Hom.: 13

Bravo AF: 0.0287

Asia WGS AF: 0.0680 AC: 239 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.28
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: rs3798676; hg19: chr6-154364139;