NM_000914.5:c.*3423T>C

Variant names:

• chr6-154122144-T-C
• rs613341
• NM_000914.5:c.*3423T>C

Variant summary

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

The NM_000914.5(OPRM1):​c.*3423T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,226 control chromosomes in the GnomAD database, including 63,911 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 0.92 (63911 hom., cov: 33)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.*3423T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.*3423T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_000914.5	ENSP00000328264.7
OPRM1	ENST00000337049.8	c.1164+30672T>C		intron_variant	Intron 3 of 3	1		ENSP00000338381.4
OPRM1	ENST00000524150.2	n.*250+30672T>C		intron_variant	Intron 2 of 2	5		ENSP00000430575.1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139334 AN: 152108 Hom.: 63860 Cov.: 33

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.920

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

GnomAD4 genome AF: 0.916 AC: 139444 AN: 152226 Hom.: 63911 Cov.: 33 AF XY: 0.917 AC XY: 68210 AN XY: 74422

African (AFR) AF: 0.923 AC: 38361 AN: 41560

American (AMR) AF: 0.935 AC: 14275 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3082 AN: 3470

East Asian (EAS) AF: 0.983 AC: 5096 AN: 5184

South Asian (SAS) AF: 0.974 AC: 4706 AN: 4832

European-Finnish (FIN) AF: 0.876 AC: 9275 AN: 10590

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61619 AN: 68008

Other (OTH) AF: 0.921 AC: 1945 AN: 2112

Alfa AF: 0.911 Hom.: 22802

Bravo AF: 0.921

Asia WGS AF: 0.975 AC: 3391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.56
PhyloP100		-0.36
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: rs613341; hg19: chr6-154443279;