ENST00000522236.1:c.-248G>A

Variant names:

• chr6-154087567-G-A
• rs9322446
• ENST00000522236.1:c.-248G>A

Variant summary

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

The ENST00000522236.1(OPRM1):​c.-248G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 984,764 control chromosomes in the GnomAD database, including 11,629 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 0.12 (1359 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10270 hom.)
• Consequence: OPRM1 ENST00000522236.1 5_prime_UTR
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.357
• Publications: 19 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]

ENSG00000299884 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522236.1. 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.291-2259G>A		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145287.3		c.-248G>A		5_prime_UTR	Exon 1 of 4	NP_001138759.1	P35372-12
	OPRM1	NM_001285526.2		c.-229G>A		5_prime_UTR	Exon 1 of 4	NP_001272455.1	P35372-12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000522236.1	TSL:1	c.-248G>A		5_prime_UTR	Exon 1 of 4	ENSP00000429373.1	P35372-12
	OPRM1	ENST00000522555.5	TSL:1	c.-229G>A		5_prime_UTR	Exon 1 of 4	ENSP00000429719.1	P35372-12
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.291-2259G>A		intron	N/A	ENSP00000328264.7	P35372-1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18272 AN: 152054 Hom.: 1360 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.155 AC: 128781 AN: 832592 Hom.: 10270 Cov.: 31 AF XY: 0.154 AC XY: 59398 AN XY: 384510

African (AFR) AF: 0.0509 AC: 803 AN: 15784

American (AMR) AF: 0.0752 AC: 74 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 428 AN: 5150

East Asian (EAS) AF: 0.0369 AC: 134 AN: 3630

South Asian (SAS) AF: 0.0651 AC: 1072 AN: 16458

European-Finnish (FIN) AF: 0.216 AC: 60 AN: 278

Middle Eastern (MID) AF: 0.0952 AC: 154 AN: 1618

European-Non Finnish (NFE) AF: 0.161 AC: 122532 AN: 761406

Other (OTH) AF: 0.129 AC: 3524 AN: 27284

GnomAD4 genome AF: 0.120 AC: 18267 AN: 152172 Hom.: 1359 Cov.: 32 AF XY: 0.121 AC XY: 9008 AN XY: 74382

African (AFR) AF: 0.0598 AC: 2485 AN: 41528

American (AMR) AF: 0.0925 AC: 1414 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5188

South Asian (SAS) AF: 0.0587 AC: 283 AN: 4822

European-Finnish (FIN) AF: 0.249 AC: 2630 AN: 10570

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10625 AN: 67992

Other (OTH) AF: 0.111 AC: 234 AN: 2110

Alfa AF: 0.131 Hom.: 353

Bravo AF: 0.109

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.46
DANN	Benign	0.66
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9322446; hg19: chr6-154408702;