6-154092293-A-G

Position:

• chr6-154092293-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000914.5(OPRM1):​c.1164+821A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 152,254 control chromosomes in the GnomAD database, including 70,364 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 0.96 (70364 hom., cov: 31)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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]

OPRM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+821A>G		intron_variant		ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1164+821A>G		intron_variant		1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146215 AN: 152136 Hom.: 70304 Cov.: 31

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.961 AC: 146334 AN: 152254 Hom.: 70364 Cov.: 31 AF XY: 0.962 AC XY: 71632 AN XY: 74424

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.958

Alfa AF: 0.951 Hom.: 22544

Bravo AF: 0.963

Asia WGS AF: 0.993 AC: 3447 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs510587; hg19: chr6-154413428; COSMIC: COSV57683327; COSMIC: COSV57683327;