6-154084595-A-T

Variant names:

• chr6-154084595-A-T
• rs3778158
• NM_000914.5:c.291-5231A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000914.5(OPRM1):​c.291-5231A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,232 control chromosomes in the GnomAD database, including 2,121 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 0.16 (2121 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 6 publications found

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]

ENSG00000299884 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.291-5231A>T		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.570-5231A>T		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.570-5231A>T		intron	N/A	NP_001272453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.291-5231A>T		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.570-5231A>T		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.477-5231A>T		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24623 AN: 152114 Hom.: 2116 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.162 AC: 24657 AN: 152232 Hom.: 2121 Cov.: 32 AF XY: 0.158 AC XY: 11771 AN XY: 74428

African (AFR) AF: 0.189 AC: 7833 AN: 41534

American (AMR) AF: 0.125 AC: 1907 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3470

East Asian (EAS) AF: 0.0444 AC: 230 AN: 5182

South Asian (SAS) AF: 0.0455 AC: 220 AN: 4832

European-Finnish (FIN) AF: 0.176 AC: 1861 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11618 AN: 68012

Other (OTH) AF: 0.146 AC: 309 AN: 2116

Alfa AF: 0.166 Hom.: 248

Bravo AF: 0.159

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.47
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3778158; hg19: chr6-154405730;