6-154097012-T-C

Variant names:

• chr6-154097012-T-C
• rs548646
• NM_000914.5:c.1164+5540T>C

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+5540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,124 control chromosomes in the GnomAD database, including 32,532 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 0.65 (32532 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 21 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+5540T>C		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+5540T>C		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98612 AN: 152006 Hom.: 32537 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.648 AC: 98636 AN: 152124 Hom.: 32532 Cov.: 33 AF XY: 0.656 AC XY: 48808 AN XY: 74372

African (AFR) AF: 0.543 AC: 22525 AN: 41488

American (AMR) AF: 0.725 AC: 11072 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4664 AN: 5188

South Asian (SAS) AF: 0.829 AC: 3998 AN: 4824

European-Finnish (FIN) AF: 0.688 AC: 7273 AN: 10572

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44511 AN: 67990

Other (OTH) AF: 0.687 AC: 1448 AN: 2108

Alfa AF: 0.661 Hom.: 24813

Bravo AF: 0.649

Asia WGS AF: 0.839 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.46
PhyloP100		-0.98
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: rs548646; hg19: chr6-154418147;