ENST00000452687.6:c.*19G>A

Variant names:

• chr6-154110430-G-A
• rs606545
• ENST00000452687.6:c.*19G>A

Variant summary

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

The ENST00000452687.6(OPRM1):​c.*19G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,457,050 control chromosomes in the GnomAD database, including 37,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (3500 hom., cov: 30)
  • Exomes 𝑓: 0.22 (34254 hom.)
• Consequence: OPRM1 ENST00000452687.6 3_prime_UTR
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.715
• Publications: 10 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 (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1165-8253G>A		intron_variant	Intron 3 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1165-8253G>A		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31475 AN: 151876 Hom.: 3497 Cov.: 30

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.190

GnomAD2 exomes AF: 0.195 AC: 29701 AN: 152462 AF XY: 0.196

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0962

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.224 AC: 292139 AN: 1305056 Hom.: 34254 Cov.: 21 AF XY: 0.223 AC XY: 144950 AN XY: 648652

African (AFR) AF: 0.156 AC: 4656 AN: 29800

American (AMR) AF: 0.151 AC: 5285 AN: 35102

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 4849 AN: 24452

East Asian (EAS) AF: 0.0858 AC: 3028 AN: 35294

South Asian (SAS) AF: 0.156 AC: 12059 AN: 77420

European-Finnish (FIN) AF: 0.198 AC: 9723 AN: 49048

Middle Eastern (MID) AF: 0.271 AC: 1490 AN: 5498

European-Non Finnish (NFE) AF: 0.241 AC: 239221 AN: 993480

Other (OTH) AF: 0.215 AC: 11828 AN: 54962

GnomAD4 genome AF: 0.207 AC: 31508 AN: 151994 Hom.: 3500 Cov.: 30 AF XY: 0.202 AC XY: 14983 AN XY: 74270

African (AFR) AF: 0.170 AC: 7039 AN: 41434

American (AMR) AF: 0.190 AC: 2899 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3470

East Asian (EAS) AF: 0.0846 AC: 437 AN: 5166

South Asian (SAS) AF: 0.146 AC: 703 AN: 4816

European-Finnish (FIN) AF: 0.188 AC: 1982 AN: 10524

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

European-Non Finnish (NFE) AF: 0.251 AC: 17050 AN: 67992

Other (OTH) AF: 0.192 AC: 406 AN: 2110

Alfa AF: 0.211 Hom.: 1053

Bravo AF: 0.204

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.7
DANN	Benign	0.39
PhyloP100		0.71
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: rs606545; hg19: chr6-154431565; COSMIC: COSV57822672; COSMIC: COSV57822672;