6-154084916-A-G

Position:

• chr6-154084916-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.291-4910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 134,808 control chromosomes in the GnomAD database, including 1,924 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 0.18 (1924 hom., cov: 30)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.291-4910A>G		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.291-4910A>G		intron_variant		1	NM_000914.5	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 23585 AN: 134720 Hom.: 1919 Cov.: 30

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.175 AC: 23619 AN: 134808 Hom.: 1924 Cov.: 30 AF XY: 0.172 AC XY: 11274 AN XY: 65532

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0493

Gnomad4 SAS AF: 0.0478

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.164

Alfa AF: 0.116 Hom.: 269

Bravo AF: 0.153

Asia WGS AF: 0.0460 AC: 159 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs3798678; hg19: chr6-154406051;