rs550014

Positions:

• chr6-154113759-T-C

Variant summary

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

The ENST00000330432.12(OPRM1):​c.1165-4924T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,156 control chromosomes in the GnomAD database, including 3,486 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 0.21 (3486 hom., cov: 32)
• Consequence: OPRM1 ENST00000330432.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1165-4924T>C		intron_variant		ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1165-4924T>C		intron_variant		1	NM_000914.5	ENSP00000328264	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31417 AN: 152038 Hom.: 3483 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.207 AC: 31450 AN: 152156 Hom.: 3486 Cov.: 32 AF XY: 0.201 AC XY: 14966 AN XY: 74390

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0843

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.192

Alfa AF: 0.223 Hom.: 601

Bravo AF: 0.204

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs550014; hg19: chr6-154434894;