chr6-154076193-A-G

Variant names:

• chr6-154076193-A-G
• rs483021
• NM_000914.5:c.291-13633A>G

Variant summary

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

The NM_001145279.4(OPRM1):​c.570-13633A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,274 control chromosomes in the GnomAD database, including 325 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 0.048 (325 hom., cov: 32)
• Consequence: OPRM1 NM_001145279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.146 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.291-13633A>G		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.570-13633A>G		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.570-13633A>G		intron	N/A	NP_001272453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.291-13633A>G		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.570-13633A>G		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.477-13633A>G		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7226 AN: 152156 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0476 AC: 7243 AN: 152274 Hom.: 325 Cov.: 32 AF XY: 0.0478 AC XY: 3563 AN XY: 74472

African (AFR) AF: 0.0208 AC: 865 AN: 41564

American (AMR) AF: 0.151 AC: 2304 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 298 AN: 3472

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

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4826

European-Finnish (FIN) AF: 0.0344 AC: 365 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0452 AC: 3074 AN: 68010

Other (OTH) AF: 0.0751 AC: 159 AN: 2116

Alfa AF: 0.0496 Hom.: 33

Bravo AF: 0.0580

Asia WGS AF: 0.0240 AC: 84 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.73
PhyloP100		0.25
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: rs483021; hg19: chr6-154397328;