chr6-154103824-T-C

Variant names:

• chr6-154103824-T-C
• rs609623
• NM_000914.5:c.1164+12352T>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.1164+12352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,992 control chromosomes in the GnomAD database, including 34,857 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 0.67 (34857 hom., cov: 30)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000914.5. 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.1164+12352T>C		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.1443+12352T>C		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.1443+12352T>C		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.1164+12352T>C		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.1443+12352T>C		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000419506.6	TSL:1	c.1165-3641T>C		intron	N/A	ENSP00000403549.2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102467 AN: 151874 Hom.: 34854 Cov.: 30

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.674 AC: 102511 AN: 151992 Hom.: 34857 Cov.: 30 AF XY: 0.681 AC XY: 50619 AN XY: 74290

African (AFR) AF: 0.637 AC: 26371 AN: 41408

American (AMR) AF: 0.731 AC: 11167 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2392 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4647 AN: 5172

South Asian (SAS) AF: 0.829 AC: 3996 AN: 4820

European-Finnish (FIN) AF: 0.687 AC: 7253 AN: 10558

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44447 AN: 67970

Other (OTH) AF: 0.702 AC: 1483 AN: 2112

Alfa AF: 0.653 Hom.: 3843

Bravo AF: 0.678

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.79
PhyloP100		0.29
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: rs609623; hg19: chr6-154424959;