rs506247

Variant names:

• chr6-154074792-A-C
• rs506247
• NM_000914.5:c.291-15034A>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.291-15034A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 152,166 control chromosomes in the GnomAD database, including 324 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 0.047 (324 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.291-15034A>C		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.291-15034A>C		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7174 AN: 152048 Hom.: 316 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0473 AC: 7191 AN: 152166 Hom.: 324 Cov.: 32 AF XY: 0.0477 AC XY: 3547 AN XY: 74420

African (AFR) AF: 0.0207 AC: 861 AN: 41538

American (AMR) AF: 0.150 AC: 2298 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0252 AC: 121 AN: 4808

European-Finnish (FIN) AF: 0.0345 AC: 366 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0446 AC: 3030 AN: 67974

Other (OTH) AF: 0.0754 AC: 159 AN: 2110

Alfa AF: 0.0492 Hom.: 34

Bravo AF: 0.0575

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		0.54
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: rs506247; hg19: chr6-154395927;