ENST00000523520.1:n.1103A>G

Variant names:

• chr6-154074024-A-G
• rs9478504
• ENST00000523520.1:n.1103A>G

Variant summary

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

The ENST00000523520.1(OPRM1):​n.1103A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,212 control chromosomes in the GnomAD database, including 1,858 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 0.15 (1858 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OPRM1 ENST00000523520.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.291-15802A>G		intron_variant	Intron 1 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.291-15802A>G		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23295 AN: 152094 Hom.: 1858 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.146

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.153 AC: 23299 AN: 152212 Hom.: 1858 Cov.: 32 AF XY: 0.149 AC XY: 11117 AN XY: 74418

African (AFR) AF: 0.154 AC: 6410 AN: 41532

American (AMR) AF: 0.123 AC: 1875 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5182

South Asian (SAS) AF: 0.0507 AC: 245 AN: 4828

European-Finnish (FIN) AF: 0.176 AC: 1867 AN: 10596

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11660 AN: 67990

Other (OTH) AF: 0.143 AC: 302 AN: 2116

Alfa AF: 0.164 Hom.: 259

Bravo AF: 0.150

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		0.010
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: rs9478504; hg19: chr6-154395159;