rs17180961

Positions:

• chr6-154037503-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000434900.6(OPRM1):​c.1-1658C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 152,024 control chromosomes in the GnomAD database, including 35 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 0.016 (35 hom., cov: 32)
• Consequence: OPRM1 ENST00000434900.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (2489/152024) while in subpopulation NFE AF= 0.0271 (1840/67900). AF 95% confidence interval is 0.0261. There are 35 homozygotes in gnomad4. There are 1112 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_001145279.4	c.1-1658C>A		intron_variant
OPRM1	NM_001145280.4	c.-11+26485C>A		intron_variant
OPRM1	NM_001145281.3	c.47+26944C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000434900.6	c.1-1658C>A		intron_variant		1
OPRM1	ENST00000518759.5	c.47+26944C>A		intron_variant		1
OPRM1	ENST00000520282.5	c.11-1908C>A		intron_variant		1
OPRM1	ENST00000520708.5	c.-11+26485C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2491 AN: 151906 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0149

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

GnomAD4 genome AF: 0.0164 AC: 2489 AN: 152024 Hom.: 35 Cov.: 32 AF XY: 0.0150 AC XY: 1112 AN XY: 74304

Gnomad4 AFR AF: 0.00448

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0207 Hom.: 6

Bravo AF: 0.0158

Asia WGS AF: 0.00376 AC: 13 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17180961; hg19: chr6-154358638;