rs13195018

Variant names:

• chr6-154137816-A-C
• rs13195018
• ENST00000337049.8:c.1164+46344A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-154137816-A-C
• chr6-154137816-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337049.8(OPRM1):​c.1164+46344A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,110 control chromosomes in the GnomAD database, including 4,566 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 0.24 (4566 hom., cov: 32)
• Consequence: OPRM1 ENST00000337049.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_001008503.3	c.1164+46344A>C		intron_variant	Intron 3 of 3		NP_001008503.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000337049.8	c.1164+46344A>C		intron_variant	Intron 3 of 3	1		ENSP00000338381.4
OPRM1	ENST00000524150.2	n.*250+46344A>C		intron_variant	Intron 2 of 2	5		ENSP00000430575.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36214 AN: 151992 Hom.: 4552 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.238 AC: 36272 AN: 152110 Hom.: 4566 Cov.: 32 AF XY: 0.233 AC XY: 17367 AN XY: 74378

African (AFR) AF: 0.300 AC: 12450 AN: 41488

American (AMR) AF: 0.194 AC: 2959 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3470

East Asian (EAS) AF: 0.0850 AC: 441 AN: 5186

South Asian (SAS) AF: 0.142 AC: 684 AN: 4828

European-Finnish (FIN) AF: 0.188 AC: 1986 AN: 10562

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16365 AN: 67968

Other (OTH) AF: 0.207 AC: 439 AN: 2116

Alfa AF: 0.249 Hom.: 632

Bravo AF: 0.240

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.033
DANN	Benign	0.62
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13195018; hg19: chr6-154458951;