rs497332

Variant names:

• chr6-154110258-C-G
• rs497332
• NM_000914.5:c.1165-8425C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-154110258-C-G
• chr6-154110258-C-A
• chr6-154110258-C-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.1165-8425C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 643,296 control chromosomes in the GnomAD database, including 271,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.92 (63953 hom., cov: 32)
  • Exomes 𝑓: 0.92 (207073 hom.)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.206
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 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.1165-8425C>G		intron	N/A	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.1444-8425C>G		intron	N/A	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.1444-8425C>G		intron	N/A	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.1165-8425C>G		intron	N/A	ENSP00000328264.7	P35372-1
	OPRM1	ENST00000434900.6	TSL:1	c.1444-8425C>G		intron	N/A	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000337049.8	TSL:1	c.1164+18786C>G		intron	N/A	ENSP00000338381.4	P35372-5

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139389 AN: 152114 Hom.: 63902 Cov.: 32

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.922

GnomAD4 exome AF: 0.918 AC: 450659 AN: 491064 Hom.: 207073 AF XY: 0.921 AC XY: 238373 AN XY: 258952

African (AFR) AF: 0.929 AC: 10910 AN: 11744

American (AMR) AF: 0.927 AC: 14786 AN: 15946

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 13038 AN: 14652

East Asian (EAS) AF: 0.979 AC: 27407 AN: 28004

South Asian (SAS) AF: 0.976 AC: 42780 AN: 43850

European-Finnish (FIN) AF: 0.884 AC: 38511 AN: 43586

Middle Eastern (MID) AF: 0.959 AC: 2133 AN: 2224

European-Non Finnish (NFE) AF: 0.908 AC: 276964 AN: 304902

Other (OTH) AF: 0.923 AC: 24130 AN: 26156

GnomAD4 genome AF: 0.916 AC: 139499 AN: 152232 Hom.: 63953 Cov.: 32 AF XY: 0.917 AC XY: 68247 AN XY: 74432

African (AFR) AF: 0.924 AC: 38375 AN: 41540

American (AMR) AF: 0.936 AC: 14315 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3084 AN: 3472

East Asian (EAS) AF: 0.983 AC: 5083 AN: 5172

South Asian (SAS) AF: 0.974 AC: 4696 AN: 4820

European-Finnish (FIN) AF: 0.877 AC: 9277 AN: 10584

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61634 AN: 68026

Other (OTH) AF: 0.923 AC: 1950 AN: 2112

Alfa AF: 0.891 Hom.: 2862

Bravo AF: 0.921

Asia WGS AF: 0.975 AC: 3389 AN: 3476

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.57
PhyloP100		0.21
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: rs497332; hg19: chr6-154431393;