rs10485057

Positions:

• chr6-154092120-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+648A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,162 control chromosomes in the GnomAD database, including 955 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 0.11 (955 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.1164+648A>G		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.1164+648A>G		intron_variant		1	NM_000914.5	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16086 AN: 152048 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.106 AC: 16124 AN: 152162 Hom.: 955 Cov.: 32 AF XY: 0.105 AC XY: 7827 AN XY: 74388

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0942

Gnomad4 OTH AF: 0.0929

Alfa AF: 0.0974 Hom.: 212

Bravo AF: 0.104

Asia WGS AF: 0.0360 AC: 125 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.5
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10485057; hg19: chr6-154413255;