6-154100709-G-T

Variant names:

• chr6-154100709-G-T
• rs1323042
• NM_000914.5:c.1164+9237G>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.1164+9237G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,130 control chromosomes in the GnomAD database, including 19,175 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 0.49 (19175 hom., cov: 30)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+9237G>T		intron_variant	Intron 3 of 3	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.1164+9237G>T		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74593 AN: 151016 Hom.: 19180 Cov.: 30

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.494 AC: 74596 AN: 151130 Hom.: 19175 Cov.: 30 AF XY: 0.501 AC XY: 36999 AN XY: 73792

African (AFR) AF: 0.367 AC: 15153 AN: 41268

American (AMR) AF: 0.487 AC: 7375 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1953 AN: 3462

East Asian (EAS) AF: 0.796 AC: 4103 AN: 5154

South Asian (SAS) AF: 0.652 AC: 3133 AN: 4804

European-Finnish (FIN) AF: 0.587 AC: 6081 AN: 10356

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35125 AN: 67634

Other (OTH) AF: 0.524 AC: 1099 AN: 2096

Alfa AF: 0.497 Hom.: 2388

Bravo AF: 0.483

Asia WGS AF: 0.695 AC: 2399 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.28
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1323042; hg19: chr6-154421844;