rs9478499

Variant names:

• chr6-154024154-T-A
• rs9478499
• ENST00000434900.6:c.-1+13136T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145279.4(OPRM1):​c.-1+13136T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,100 control chromosomes in the GnomAD database, including 1,456 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 0.13 (1456 hom., cov: 32)
• Consequence: OPRM1 NM_001145279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145279.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_001145279.4		c.-1+13136T>A		intron	N/A	NP_001138751.1
	OPRM1	NM_001145281.3		c.47+13595T>A		intron	N/A	NP_001138753.1
	OPRM1	NM_001145280.4		c.-11+13136T>A		intron	N/A	NP_001138752.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.-1+13136T>A		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000518759.5	TSL:1	c.47+13595T>A		intron	N/A	ENSP00000430260.1
	OPRM1	ENST00000520708.5	TSL:1	c.-11+13136T>A		intron	N/A	ENSP00000430876.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20347 AN: 151982 Hom.: 1455 Cov.: 32

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.134 AC: 20351 AN: 152100 Hom.: 1456 Cov.: 32 AF XY: 0.131 AC XY: 9746 AN XY: 74360

African (AFR) AF: 0.0941 AC: 3910 AN: 41552

American (AMR) AF: 0.114 AC: 1747 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3468

East Asian (EAS) AF: 0.0464 AC: 240 AN: 5176

South Asian (SAS) AF: 0.0434 AC: 209 AN: 4820

European-Finnish (FIN) AF: 0.193 AC: 2043 AN: 10584

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

European-Non Finnish (NFE) AF: 0.166 AC: 11300 AN: 67922

Other (OTH) AF: 0.120 AC: 254 AN: 2108

Alfa AF: 0.151 Hom.: 220

Bravo AF: 0.127

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.40
PhyloP100		0.13
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: rs9478499; hg19: chr6-154345289;