NM_000914.5:c.290+16956T>C

Variant names:

• chr6-154056790-T-C
• rs3778146
• NM_000914.5:c.290+16956T>C

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+16956T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,012 control chromosomes in the GnomAD database, including 1,688 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 0.14 (1688 hom., cov: 31)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.290+16956T>C		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.569+16956T>C		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.569+16956T>C		intron	N/A	NP_001272453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.290+16956T>C		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.569+16956T>C		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.476+16956T>C		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21945 AN: 151894 Hom.: 1688 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.144 AC: 21948 AN: 152012 Hom.: 1688 Cov.: 31 AF XY: 0.141 AC XY: 10461 AN XY: 74310

African (AFR) AF: 0.120 AC: 4975 AN: 41482

American (AMR) AF: 0.117 AC: 1789 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.0458 AC: 236 AN: 5148

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2065 AN: 10536

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11696 AN: 67968

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.158 Hom.: 2579

Bravo AF: 0.137

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.39
PhyloP100		-0.24
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: rs3778146; hg19: chr6-154377925;