rs514980

Variant names:

• chr6-154047032-T-C
• rs514980
• NM_000914.5:c.290+7198T>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+7198T>C 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 152,044 control chromosomes in the GnomAD database, including 2,911 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 (2911 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78
• Publications: 13 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+7198T>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.290+7198T>C		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28201 AN: 151926 Hom.: 2901 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.186 AC: 28223 AN: 152044 Hom.: 2911 Cov.: 32 AF XY: 0.183 AC XY: 13579 AN XY: 74324

African (AFR) AF: 0.122 AC: 5076 AN: 41488

American (AMR) AF: 0.266 AC: 4066 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3470

East Asian (EAS) AF: 0.0467 AC: 241 AN: 5166

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4816

European-Finnish (FIN) AF: 0.230 AC: 2429 AN: 10560

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14656 AN: 67958

Other (OTH) AF: 0.201 AC: 424 AN: 2106

Alfa AF: 0.205 Hom.: 1897

Bravo AF: 0.189

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.55
DANN	Benign	0.33
PhyloP100		-3.8
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: rs514980; hg19: chr6-154368167;