6-154121541-G-T

Variant names:

• chr6-154121541-G-T
• rs642489
• NM_000914.5:c.*2820G>T

Variant summary

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

The NM_000914.5(OPRM1):​c.*2820G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,146 control chromosomes in the GnomAD database, including 3,210 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 0.20 (3210 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.247 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.*2820G>T		3_prime_UTR	Exon 4 of 4	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.*2820G>T		3_prime_UTR	Exon 6 of 6	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.*2820G>T		3_prime_UTR	Exon 5 of 5	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.*2820G>T		3_prime_UTR	Exon 4 of 4	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000337049.8	TSL:1	c.1164+30069G>T		intron	N/A	ENSP00000338381.4	P35372-5
	OPRM1	ENST00000524150.2	TSL:5	n.*250+30069G>T		intron	N/A	ENSP00000430575.1	P35372-18

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29705 AN: 152028 Hom.: 3208 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0841

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.195 AC: 29730 AN: 152146 Hom.: 3210 Cov.: 33 AF XY: 0.191 AC XY: 14176 AN XY: 74358

African (AFR) AF: 0.129 AC: 5366 AN: 41538

American (AMR) AF: 0.185 AC: 2826 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3472

East Asian (EAS) AF: 0.0841 AC: 436 AN: 5182

South Asian (SAS) AF: 0.146 AC: 702 AN: 4816

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10582

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17027 AN: 67970

Other (OTH) AF: 0.181 AC: 381 AN: 2108

Alfa AF: 0.143 Hom.: 374

Bravo AF: 0.191

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.71
DANN	Benign	0.42
PhyloP100		0.19
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: rs642489; hg19: chr6-154442676;