rs599548

Variant names:

• chr6-154097426-G-A
• rs599548
• NM_000914.5:c.1164+5954G>A

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+5954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,004 control chromosomes in the GnomAD database, including 1,457 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 0.13 (1457 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 8 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+5954G>A		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+5954G>A		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19766 AN: 151886 Hom.: 1446 Cov.: 33

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.130 AC: 19784 AN: 152004 Hom.: 1457 Cov.: 33 AF XY: 0.131 AC XY: 9712 AN XY: 74292

African (AFR) AF: 0.0929 AC: 3852 AN: 41464

American (AMR) AF: 0.229 AC: 3486 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3468

East Asian (EAS) AF: 0.102 AC: 529 AN: 5180

South Asian (SAS) AF: 0.175 AC: 842 AN: 4822

European-Finnish (FIN) AF: 0.0991 AC: 1043 AN: 10526

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9113 AN: 67972

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.149 Hom.: 958

Bravo AF: 0.139

Asia WGS AF: 0.135 AC: 469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		0.036
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: rs599548; hg19: chr6-154418561; COSMIC: COSV57674333; COSMIC: COSV57674333;