rs511420

Variant names:

• chr6-154102897-T-C
• rs511420
• NM_000914.5:c.1164+11425T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-154102897-T-C
• chr6-154102897-T-G

Variant summary

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

The NM_000914.5(OPRM1):​c.1164+11425T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 149,510 control chromosomes in the GnomAD database, including 1,032 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 0.11 (1032 hom., cov: 28)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.1164+11425T>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.1164+11425T>C		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16106 AN: 149404 Hom.: 1029 Cov.: 28

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0167

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0577

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.108 AC: 16138 AN: 149510 Hom.: 1032 Cov.: 28 AF XY: 0.106 AC XY: 7732 AN XY: 72844

African (AFR) AF: 0.162 AC: 6490 AN: 40172

American (AMR) AF: 0.0753 AC: 1134 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3460

East Asian (EAS) AF: 0.0167 AC: 86 AN: 5148

South Asian (SAS) AF: 0.0252 AC: 120 AN: 4758

European-Finnish (FIN) AF: 0.112 AC: 1114 AN: 9916

Middle Eastern (MID) AF: 0.0556 AC: 16 AN: 288

European-Non Finnish (NFE) AF: 0.0952 AC: 6444 AN: 67722

Other (OTH) AF: 0.0999 AC: 208 AN: 2082

Alfa AF: 0.0688 Hom.: 89

Bravo AF: 0.109

Asia WGS AF: 0.0300 AC: 104 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		-0.83
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: rs511420; hg19: chr6-154424032;