NM_000914.5:c.290+7817T>C

Variant names:

• chr6-154047651-T-C
• rs509544
• NM_000914.5:c.290+7817T>C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_000914.5(OPRM1):c.290+7817T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene OPRM1 is a tumor suppressor gene (CancerMine: 1 TSG, 2 oncogene citations). The gene OPRM1 is a known oncogene (CancerMine: 1 TSG, 2 oncogene citations). The variant allele was found at a cumulative frequency of 0.186 (AC=28,357) in the gnomAD database across 152,184 control chromosomes, including 2,949 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.26. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2949 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 5 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]

ENSG00000299863 (HGNC:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.26 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000914.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	OPRM1 NM_000914.5	MANE Select	c.290+7817T>C	intron	Intron 1 of 3	Prot: NP_000905.3 UniProt:
	OPRM1 NM_001145279.4		c.569+7817T>C	intron	Intron 3 of 5	Prot: NP_001138751.1 UniProt:
	OPRM1 NM_001285524.1		c.569+7817T>C	intron	Intron 2 of 4	Prot: NP_001272453.1 UniProt:

OPRM1 NM_000914.5

MANE Select

HGVSc / HGVSpc.290+7817T>C

Exon rankIntron 1 of 3

intron

Prot: NP_000905.3UniProt: P35372-1

OPRM1 NM_001145279.4

HGVSc / HGVSpc.569+7817T>C

Exon rankIntron 3 of 5

intron

Prot: NP_001138751.1UniProt: P35372-10

OPRM1 NM_001285524.1

HGVSc / HGVSpc.569+7817T>C

Exon rankIntron 2 of 4

intron

Prot: NP_001272453.1UniProt: P35372-10

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	OPRM1 ENST00000330432.12	TSL:1MANE Select	c.290+7817T>C	intron	Intron 1 of 3	Prot: ENSP00000328264.7 UniProt:
	OPRM1 ENST00000434900.6	TSL:1	c.569+7817T>C	intron	Intron 3 of 5	Prot: ENSP00000394624.2 UniProt:
	OPRM1 ENST00000360422.8	TSL:1	c.476+7817T>C	intron	Intron 1 of 3	Prot: ENSP00000353598.5 UniProt:

OPRM1 ENST00000330432.12

TSL:1MANE Select

HGVSc / HGVSpc.290+7817T>C

Exon rankIntron 1 of 3

intron

Prot: ENSP00000328264.7UniProt: P35372-1

OPRM1 ENST00000434900.6

TSL:1

HGVSc / HGVSpc.569+7817T>C

Exon rankIntron 3 of 5

intron

Prot: ENSP00000394624.2UniProt: P35372-10

OPRM1 ENST00000360422.8

TSL:1

HGVSc / HGVSpc.476+7817T>C

Exon rankIntron 1 of 3

intron

Prot: ENSP00000353598.5UniProt: A0A0A0MRG7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.186	AC:28334	Hom:2940	AN:152066	Cov:32
GnomAD4 genome	AF: 0.186	AC:28357	Hom:2949	AN:152184	Cov:32
TOPMed (Bravo)	AF: 0.189	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.202	AC:42308	Hom:4672	AN:209126	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.199	AC:467	Hom:43	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0541	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.200	AC:60	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.0680	AC:236	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0500	AC:363	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.102	AC:18	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0358	AC:4398	Hom:103	AN:122770	Cov:
Turkish Variome	AF: 0.166	AC:257	Hom:21	AN:1546	Cov:
UK10K	AF: 0.208	AC:1571	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0516	AC:462	Hom:18	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.4
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.61
GPN-Star LLR	N/A	2.9
GPN-Star score	N/A	-1.6
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.28

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs509544;

hg19: chr6-154368786;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar