chr6-154059015-T-G

Position:

• chr6-154059015-T-G

Variant summary

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

The NM_000914.5(OPRM1):​c.290+19181T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 152,250 control chromosomes in the GnomAD database, including 468 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 0.066 (468 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+19181T>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.290+19181T>G		intron_variant		1	NM_000914.5	ENSP00000328264	P1

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10051 AN: 152132 Hom.: 464 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0463

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

GnomAD4 genome AF: 0.0660 AC: 10056 AN: 152250 Hom.: 468 Cov.: 32 AF XY: 0.0648 AC XY: 4824 AN XY: 74442

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0270

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.0943

Gnomad4 SAS AF: 0.0644

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0441

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0550 Hom.: 40

Bravo AF: 0.0688

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7748401; hg19: chr6-154380150;