ENST00000434900.6:c.1-12053T>G

Variant names:

• chr6-154027108-T-G
• rs7776131
• ENST00000434900.6:c.1-12053T>G

Variant summary

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

The ENST00000434900.6(OPRM1):​c.1-12053T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,230 control chromosomes in the GnomAD database, including 1,072 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 0.089 (1072 hom., cov: 32)
• Consequence: OPRM1 ENST00000434900.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434900.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_001145279.4		c.1-12053T>G		intron	N/A	NP_001138751.1
	OPRM1	NM_001145281.3		c.47+16549T>G		intron	N/A	NP_001138753.1
	OPRM1	NM_001145280.4		c.-11+16090T>G		intron	N/A	NP_001138752.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.1-12053T>G		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000518759.5	TSL:1	c.47+16549T>G		intron	N/A	ENSP00000430260.1
	OPRM1	ENST00000520708.5	TSL:1	c.-11+16090T>G		intron	N/A	ENSP00000430876.1

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13493 AN: 152112 Hom.: 1068 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0440

Gnomad OTH AF: 0.0609

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

GnomAD4 genome AF: 0.0888 AC: 13514 AN: 152230 Hom.: 1072 Cov.: 32 AF XY: 0.0874 AC XY: 6506 AN XY: 74426

African (AFR) AF: 0.208 AC: 8620 AN: 41518

American (AMR) AF: 0.0345 AC: 528 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.0912 AC: 472 AN: 5174

South Asian (SAS) AF: 0.0739 AC: 357 AN: 4830

European-Finnish (FIN) AF: 0.0299 AC: 317 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0440 AC: 2994 AN: 68016

Other (OTH) AF: 0.0607 AC: 128 AN: 2108

Alfa AF: 0.0723 Hom.: 83

Bravo AF: 0.0944

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		-1.3
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: rs7776131; hg19: chr6-154348243;