rs9282814

Variant names:

• chr6-154039487-A-C
• rs9282814
• ENST00000434900.6:c.222A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-154039487-A-C
• chr6-154039487-A-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000434900.6(OPRM1):​c.222A>C​(p.Arg74Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,412,016 control chromosomes in the GnomAD database, including 1 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: OPRM1 ENST00000434900.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=0.458 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434900.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.-58A>C		5_prime_UTR	Exon 1 of 4	NP_000905.3
	OPRM1	NM_001145279.4		c.222A>C	p.Arg74Arg	synonymous	Exon 3 of 6	NP_001138751.1
	OPRM1	NM_001285524.1		c.222A>C	p.Arg74Arg	synonymous	Exon 2 of 5	NP_001272453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.222A>C	p.Arg74Arg	synonymous	Exon 3 of 6	ENSP00000394624.2
	OPRM1	ENST00000360422.8	TSL:1	c.129A>C	p.Arg43Arg	synonymous	Exon 1 of 4	ENSP00000353598.5
	OPRM1	ENST00000520282.5	TSL:1	c.87A>C	p.Arg29Arg	synonymous	Exon 2 of 3	ENSP00000430247.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1412016 Hom.: 1 Cov.: 31 AF XY: 0.00000430 AC XY: 3 AN XY: 697664

African (AFR) AF: 0.00 AC: 0 AN: 32268

American (AMR) AF: 0.00 AC: 0 AN: 36994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.00 AC: 0 AN: 36798

South Asian (SAS) AF: 0.00 AC: 0 AN: 80366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1086106

Other (OTH) AF: 0.00 AC: 0 AN: 58544

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.46
PromoterAI		-0.031	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9282814; hg19: chr6-154360622;