ENST00000434900.6:c.1-1658C>A

Variant names:

• chr6-154037503-C-A
• rs17180961
• ENST00000434900.6:c.1-1658C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.86).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

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_001145279.4		c.1-1658C>A		intron	N/A	NP_001138751.1
	OPRM1	NM_001145281.3		c.47+26944C>A		intron	N/A	NP_001138753.1
	OPRM1	NM_001145280.4		c.-11+26485C>A		intron	N/A	NP_001138752.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.1-1658C>A		intron	N/A	ENSP00000394624.2
	OPRM1	ENST00000518759.5	TSL:1	c.47+26944C>A		intron	N/A	ENSP00000430260.1
	OPRM1	ENST00000520708.5	TSL:1	c.-11+26485C>A		intron	N/A	ENSP00000430876.1

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

African (AFR) AF: 0.00448 AC: 186 AN: 41510

American (AMR) AF: 0.0127 AC: 194 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4822

European-Finnish (FIN) AF: 0.0172 AC: 182 AN: 10570

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1840 AN: 67900

Other (OTH) AF: 0.0147 AC: 31 AN: 2104

Alfa AF: 0.0232 Hom.: 52

Bravo AF: 0.0158

Asia WGS AF: 0.00376 AC: 13 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs17180961; hg19: chr6-154358638;