6-154120729-C-T

Variant names:

• chr6-154120729-C-T
• rs558948
• NM_000914.5:c.*2008C>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.*2008C>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 0.202 in 152,074 control chromosomes in the GnomAD database, including 3,349 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 (3349 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 8 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.*2008C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.*2008C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_000914.5	ENSP00000328264.7
OPRM1	ENST00000337049.8	c.1164+29257C>T		intron_variant	Intron 3 of 3	1		ENSP00000338381.4
OPRM1	ENST00000524150.2	n.*250+29257C>T		intron_variant	Intron 2 of 2	5		ENSP00000430575.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30685 AN: 151956 Hom.: 3346 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.202 AC: 30719 AN: 152074 Hom.: 3349 Cov.: 32 AF XY: 0.197 AC XY: 14639 AN XY: 74350

African (AFR) AF: 0.153 AC: 6339 AN: 41506

American (AMR) AF: 0.188 AC: 2869 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3466

East Asian (EAS) AF: 0.0846 AC: 438 AN: 5176

South Asian (SAS) AF: 0.146 AC: 702 AN: 4824

European-Finnish (FIN) AF: 0.188 AC: 1993 AN: 10578

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 17009 AN: 67944

Other (OTH) AF: 0.187 AC: 394 AN: 2112

Alfa AF: 0.233 Hom.: 7078

Bravo AF: 0.198

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.74
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: rs558948; hg19: chr6-154441864;