rs17180968

Variant names:

• chr6-154037753-T-A
• rs17180968
• ENST00000434900.6:c.1-1408T>A

Variant summary

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

The ENST00000434900.6(OPRM1):​c.1-1408T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 152,218 control chromosomes in the GnomAD database, including 199 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 0.029 (199 hom., cov: 32)
• Consequence: OPRM1 ENST00000434900.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_001145279.4	c.1-1408T>A		intron_variant	Intron 1 of 5		NP_001138751.1
OPRM1	NM_001145281.3	c.47+27194T>A		intron_variant	Intron 1 of 3		NP_001138753.1
OPRM1	NM_001145280.4	c.-11+26735T>A		intron_variant	Intron 1 of 3		NP_001138752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000434900.6	c.1-1408T>A		intron_variant	Intron 1 of 5	1		ENSP00000394624.2
OPRM1	ENST00000518759.5	c.47+27194T>A		intron_variant	Intron 1 of 3	1		ENSP00000430260.1
OPRM1	ENST00000520708.5	c.-11+26735T>A		intron_variant	Intron 1 of 3	1		ENSP00000430876.1
OPRM1	ENST00000520282.5	c.11-1658T>A		intron_variant	Intron 1 of 2	1		ENSP00000430247.1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4374 AN: 152100 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0288 AC: 4389 AN: 152218 Hom.: 199 Cov.: 32 AF XY: 0.0280 AC XY: 2083 AN XY: 74428

African (AFR) AF: 0.100 AC: 4173 AN: 41544

American (AMR) AF: 0.0101 AC: 154 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67954

Other (OTH) AF: 0.0166 AC: 35 AN: 2108

Alfa AF: 0.0232 Hom.: 16

Bravo AF: 0.0325

Asia WGS AF: 0.00751 AC: 26 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	3.2
DANN	Benign	0.37
PhyloP100		0.59
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: rs17180968; hg19: chr6-154358888;