rs6927269

Variant names:

• chr6-154067171-T-G
• rs6927269
• NM_000914.5:c.291-22655T>G

Variant summary

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

The NM_000914.5(OPRM1):​c.291-22655T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,034 control chromosomes in the GnomAD database, including 1,561 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 0.14 (1561 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• 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=-0.93).
• 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.291-22655T>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.291-22655T>G		intron_variant	Intron 1 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20995 AN: 151916 Hom.: 1561 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.138 AC: 20999 AN: 152034 Hom.: 1561 Cov.: 32 AF XY: 0.135 AC XY: 10020 AN XY: 74332

African (AFR) AF: 0.0992 AC: 4121 AN: 41560

American (AMR) AF: 0.116 AC: 1764 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3464

East Asian (EAS) AF: 0.0458 AC: 238 AN: 5192

South Asian (SAS) AF: 0.0452 AC: 218 AN: 4826

European-Finnish (FIN) AF: 0.195 AC: 2050 AN: 10524

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

European-Non Finnish (NFE) AF: 0.172 AC: 11656 AN: 67888

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.158 Hom.: 1008

Bravo AF: 0.131

Asia WGS AF: 0.0420 AC: 146 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.26
PhyloP100		0.21
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: rs6927269; hg19: chr6-154388306;