NM_000914.5:c.291-14506T>A

Variant names:

• chr6-154075320-T-A
• rs17209711
• NM_000914.5:c.291-14506T>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.291-14506T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,116 control chromosomes in the GnomAD database, including 1,566 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 (1566 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.291-14506T>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.291-14506T>A		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21343 AN: 151998 Hom.: 1565 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.140 AC: 21347 AN: 152116 Hom.: 1566 Cov.: 32 AF XY: 0.137 AC XY: 10173 AN XY: 74374

African (AFR) AF: 0.115 AC: 4784 AN: 41502

American (AMR) AF: 0.116 AC: 1768 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3468

East Asian (EAS) AF: 0.0453 AC: 235 AN: 5186

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4824

European-Finnish (FIN) AF: 0.176 AC: 1856 AN: 10574

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11551 AN: 67966

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.155 Hom.: 219

Bravo AF: 0.136

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		0.64
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: rs17209711; hg19: chr6-154396455;