rs6910065

Variant names:

• chr6-154028566-T-C
• rs6910065
• ENST00000434900.6:c.1-10595T>C

Variant summary

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

The ENST00000434900.6(OPRM1):​c.1-10595T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,168 control chromosomes in the GnomAD database, including 1,068 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 (1068 hom., cov: 32)
• Consequence: OPRM1 ENST00000434900.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_001145279.4	c.1-10595T>C		intron_variant	Intron 1 of 5		NP_001138751.1
OPRM1	NM_001145281.3	c.47+18007T>C		intron_variant	Intron 1 of 3		NP_001138753.1
OPRM1	NM_001145280.4	c.-11+17548T>C		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.1-10595T>C		intron_variant	Intron 1 of 5	1		ENSP00000394624.2
OPRM1	ENST00000518759.5	c.47+18007T>C		intron_variant	Intron 1 of 3	1		ENSP00000430260.1
OPRM1	ENST00000520708.5	c.-11+17548T>C		intron_variant	Intron 1 of 3	1		ENSP00000430876.1
OPRM1	ENST00000520282.5	c.11-10845T>C		intron_variant	Intron 1 of 2	1		ENSP00000430247.1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13465 AN: 152050 Hom.: 1064 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0440

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0886 AC: 13486 AN: 152168 Hom.: 1068 Cov.: 32 AF XY: 0.0873 AC XY: 6497 AN XY: 74396

African (AFR) AF: 0.207 AC: 8604 AN: 41470

American (AMR) AF: 0.0344 AC: 527 AN: 15300

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

East Asian (EAS) AF: 0.0907 AC: 468 AN: 5162

South Asian (SAS) AF: 0.0730 AC: 352 AN: 4820

European-Finnish (FIN) AF: 0.0298 AC: 316 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0440 AC: 2994 AN: 68020

Other (OTH) AF: 0.0602 AC: 127 AN: 2110

Alfa AF: 0.0757 Hom.: 99

Bravo AF: 0.0944

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.52
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: rs6910065; hg19: chr6-154349701;