chr6-154053957-C-A

Variant names:

• chr6-154053957-C-A
• rs524731
• NM_000914.5:c.290+14123C>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.290+14123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,988 control chromosomes in the GnomAD database, including 2,933 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 0.19 (2933 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 21 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+14123C>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.290+14123C>A		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28207 AN: 151870 Hom.: 2925 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.186 AC: 28228 AN: 151988 Hom.: 2933 Cov.: 32 AF XY: 0.183 AC XY: 13581 AN XY: 74290

African (AFR) AF: 0.119 AC: 4944 AN: 41496

American (AMR) AF: 0.266 AC: 4072 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3470

East Asian (EAS) AF: 0.0460 AC: 238 AN: 5178

South Asian (SAS) AF: 0.0702 AC: 339 AN: 4826

European-Finnish (FIN) AF: 0.230 AC: 2424 AN: 10558

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14743 AN: 67860

Other (OTH) AF: 0.202 AC: 426 AN: 2110

Alfa AF: 0.211 Hom.: 536

Bravo AF: 0.188

Asia WGS AF: 0.0660 AC: 231 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	0.78
DANN	Benign	0.43
PhyloP100		-0.82
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: rs524731; hg19: chr6-154375092;