chr6-154057604-G-A

Variant names:

• chr6-154057604-G-A
• rs3778147
• NM_000914.5:c.290+17770G>A

Variant summary

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

The NM_001145279.4(OPRM1):​c.569+17770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,928 control chromosomes in the GnomAD database, including 1,578 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 0.14 (1578 hom., cov: 32)
• Consequence: OPRM1 NM_001145279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 5 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]

ENSG00000299863 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145279.4. 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.290+17770G>A		intron	N/A	NP_000905.3
	OPRM1	NM_001145279.4		c.569+17770G>A		intron	N/A	NP_001138751.1
	OPRM1	NM_001285524.1		c.569+17770G>A		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.290+17770G>A		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.569+17770G>A		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.476+17770G>A		intron	N/A	ENSP00000353598.5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21067 AN: 151810 Hom.: 1578 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0453

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.139 AC: 21071 AN: 151928 Hom.: 1578 Cov.: 32 AF XY: 0.135 AC XY: 10050 AN XY: 74240

African (AFR) AF: 0.0995 AC: 4122 AN: 41440

American (AMR) AF: 0.116 AC: 1767 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3468

East Asian (EAS) AF: 0.0458 AC: 238 AN: 5192

South Asian (SAS) AF: 0.0454 AC: 218 AN: 4802

European-Finnish (FIN) AF: 0.197 AC: 2066 AN: 10510

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

European-Non Finnish (NFE) AF: 0.172 AC: 11702 AN: 67938

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.155 Hom.: 249

Bravo AF: 0.131

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.5
DANN	Benign	0.67
PhyloP100		0.16
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: rs3778147; hg19: chr6-154378739;