chr6-154128715-C-A

Variant names:

• chr6-154128715-C-A
• rs613355
• NM_000914.5:c.*9994C>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.*9994C>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 0.666 in 152,040 control chromosomes in the GnomAD database, including 34,024 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 0.67 (34024 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.*9994C>A		3_prime_UTR	Exon 4 of 4	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.*9994C>A		3_prime_UTR	Exon 6 of 6	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.*9994C>A		3_prime_UTR	Exon 5 of 5	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.*9994C>A		3_prime_UTR	Exon 4 of 4	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000337049.8	TSL:1	c.1164+37243C>A		intron	N/A	ENSP00000338381.4	P35372-5
	OPRM1	ENST00000524150.2	TSL:5	n.*250+37243C>A		intron	N/A	ENSP00000430575.1	P35372-18

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101168 AN: 151922 Hom.: 34015 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.666 AC: 101214 AN: 152040 Hom.: 34024 Cov.: 32 AF XY: 0.672 AC XY: 49957 AN XY: 74330

African (AFR) AF: 0.611 AC: 25330 AN: 41438

American (AMR) AF: 0.732 AC: 11166 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3472

East Asian (EAS) AF: 0.901 AC: 4666 AN: 5176

South Asian (SAS) AF: 0.827 AC: 3986 AN: 4818

European-Finnish (FIN) AF: 0.683 AC: 7219 AN: 10574

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44213 AN: 67984

Other (OTH) AF: 0.706 AC: 1489 AN: 2108

Alfa AF: 0.664 Hom.: 18256

Bravo AF: 0.669

Asia WGS AF: 0.846 AC: 2943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.39
PhyloP100		-1.4
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: rs613355; hg19: chr6-154449850;