ENST00000419506.6:c.*4A>C

Variant names:

• chr6-154107567-A-C
• rs650245
• ENST00000419506.6:c.*4A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000419506.6(OPRM1):​c.*4A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 566,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000018 (0 hom.)
• Consequence: OPRM1 ENST00000419506.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 13 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1165-11116A>C		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.1165-11116A>C		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000660 AC: 1 AN: 151560 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000177 AC: 1 AN: 566246 Hom.: 0 Cov.: 0 AF XY: 0.00000327 AC XY: 1 AN XY: 305468

African (AFR) AF: 0.00 AC: 0 AN: 15812

American (AMR) AF: 0.00 AC: 0 AN: 34720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20030

East Asian (EAS) AF: 0.00 AC: 0 AN: 32108

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 62776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4076

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 317060

Other (OTH) AF: 0.00 AC: 0 AN: 30700

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.28
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs650245; hg19: chr6-154428702;