rs599945

Variant names:

• chr6-154121435-C-A
• rs599945
• NM_000914.5:c.*2714C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-154121435-C-A
• chr6-154121435-C-G

Variant summary

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

The NM_000914.5(OPRM1):​c.*2714C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,222 control chromosomes in the GnomAD database, including 60,101 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 0.89 (60101 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.*2714C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.*2714C>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000914.5	ENSP00000328264.7
OPRM1	ENST00000337049.8	c.1164+29963C>A		intron_variant	Intron 3 of 3	1		ENSP00000338381.4
OPRM1	ENST00000524150.2	n.*250+29963C>A		intron_variant	Intron 2 of 2	5		ENSP00000430575.1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135011 AN: 152104 Hom.: 60081 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.933

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.887 AC: 135086 AN: 152222 Hom.: 60101 Cov.: 32 AF XY: 0.888 AC XY: 66109 AN XY: 74418

African (AFR) AF: 0.826 AC: 34282 AN: 41510

American (AMR) AF: 0.924 AC: 14124 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3075 AN: 3472

East Asian (EAS) AF: 0.983 AC: 5100 AN: 5188

South Asian (SAS) AF: 0.974 AC: 4696 AN: 4822

European-Finnish (FIN) AF: 0.876 AC: 9295 AN: 10608

Middle Eastern (MID) AF: 0.932 AC: 272 AN: 292

European-Non Finnish (NFE) AF: 0.905 AC: 61542 AN: 68022

Other (OTH) AF: 0.901 AC: 1905 AN: 2114

Alfa AF: 0.888 Hom.: 11513

Bravo AF: 0.889

Asia WGS AF: 0.967 AC: 3364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.39
PhyloP100		-0.76
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: rs599945; hg19: chr6-154442570;