rs538174

Positions:

• chr6-154131402-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000914.5(OPRM1):​c.*12681T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,216 control chromosomes in the GnomAD database, including 2,759 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 0.17 (2759 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.*12681T>C		3_prime_UTR_variant	4/4	ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.*12681T>C		3_prime_UTR_variant	4/4	1	NM_000914.5	P1
OPRM1	ENST00000337049.8	c.1164+39930T>C		intron_variant		1
OPRM1	ENST00000524150.2	c.*250+39930T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26349 AN: 152098 Hom.: 2757 Cov.: 33

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.173 AC: 26368 AN: 152216 Hom.: 2759 Cov.: 33 AF XY: 0.170 AC XY: 12618 AN XY: 74432

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0817

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.165

Alfa AF: 0.222 Hom.: 1914

Bravo AF: 0.166

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs538174; hg19: chr6-154452537;