rs6936615

Variant names:

• chr6-154033965-A-G
• rs6936615
• ENST00000434900.6:c.1-5196A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-154033965-A-G
• chr6-154033965-A-T

Variant summary

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

The NM_001145279.4(OPRM1):​c.1-5196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,308 control chromosomes in the GnomAD database, including 1,656 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 0.14 (1656 hom., cov: 33)
• Consequence: OPRM1 NM_001145279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 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_001145279.4		c.1-5196A>G		intron	N/A	NP_001138751.1
	OPRM1	NM_001145281.3		c.47+23406A>G		intron	N/A	NP_001138753.1
	OPRM1	NM_001145280.4		c.-11+22947A>G		intron	N/A	NP_001138752.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.1-5196A>G		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000518759.5	TSL:1	c.47+23406A>G		intron	N/A	ENSP00000430260.1
	OPRM1	ENST00000520708.5	TSL:1	c.-11+22947A>G		intron	N/A	ENSP00000430876.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21494 AN: 152190 Hom.: 1655 Cov.: 33

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0463

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.141 AC: 21499 AN: 152308 Hom.: 1656 Cov.: 33 AF XY: 0.138 AC XY: 10298 AN XY: 74468

African (AFR) AF: 0.0984 AC: 4090 AN: 41568

American (AMR) AF: 0.117 AC: 1784 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.0468 AC: 243 AN: 5188

South Asian (SAS) AF: 0.0430 AC: 208 AN: 4832

European-Finnish (FIN) AF: 0.204 AC: 2166 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12056 AN: 68018

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.152 Hom.: 866

Bravo AF: 0.133

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.073
DANN	Benign	0.20
PhyloP100		-0.95
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: rs6936615; hg19: chr6-154355100;