ENST00000434900.6:c.-271dupC

Variant names:

• chr6-154010744-G-GC
• rs1583105465
• ENST00000434900.6:c.-271dupC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000434900.6(OPRM1):​c.-271dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000786 in 1,271,508 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: OPRM1 ENST00000434900.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_001145279.4	c.-271dupC		5_prime_UTR_variant	Exon 1 of 6		NP_001138751.1
OPRM1	NM_001145280.4	c.-281dupC		5_prime_UTR_variant	Exon 1 of 4		NP_001138752.1
OPRM1	NM_001145281.3	c.47+189dupC		intron_variant	Intron 1 of 3		NP_001138753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000434900.6	c.-271dupC		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000394624.2
OPRM1	ENST00000520708.5	c.-281dupC		5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000430876.1
OPRM1	ENST00000520282.5	c.-261dupC		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000430247.1
OPRM1	ENST00000518759.5	c.47+189dupC		intron_variant	Intron 1 of 3	1		ENSP00000430260.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.86e-7 AC: 1 AN: 1271508 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 615268

African (AFR) AF: 0.00 AC: 0 AN: 27964

American (AMR) AF: 0.00 AC: 0 AN: 19928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18680

East Asian (EAS) AF: 0.00 AC: 0 AN: 34188

South Asian (SAS) AF: 0.00 AC: 0 AN: 60604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5136

European-Non Finnish (NFE) AF: 9.78e-7 AC: 1 AN: 1022174

Other (OTH) AF: 0.00 AC: 0 AN: 52812

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs1583105465; hg19: chr6-154331879;