chr6-154099922-G-A

Variant names:

• chr6-154099922-G-A
• rs9384179
• NM_000914.5:c.1164+8450G>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.1164+8450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 141,266 control chromosomes in the GnomAD database, including 35,460 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 0.71 (35460 hom., cov: 26)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+8450G>A		intron_variant	Intron 3 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1164+8450G>A		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.706 AC: 99796 AN: 141260 Hom.: 35474 Cov.: 26

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.706 AC: 99781 AN: 141266 Hom.: 35460 Cov.: 26 AF XY: 0.713 AC XY: 48404 AN XY: 67922

African (AFR) AF: 0.748 AC: 28542 AN: 38180

American (AMR) AF: 0.743 AC: 10300 AN: 13862

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2371 AN: 3438

East Asian (EAS) AF: 0.896 AC: 4464 AN: 4980

South Asian (SAS) AF: 0.831 AC: 3859 AN: 4642

European-Finnish (FIN) AF: 0.689 AC: 4802 AN: 6974

Middle Eastern (MID) AF: 0.686 AC: 129 AN: 188

European-Non Finnish (NFE) AF: 0.655 AC: 43385 AN: 66198

Other (OTH) AF: 0.727 AC: 1398 AN: 1924

Alfa AF: 0.554 Hom.: 1397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.29
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9384179; hg19: chr6-154421057;