6-154047651-T-G

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_000914.5(OPRM1):c.290+7817T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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: not found (cov: 32)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 0 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 ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

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>G	intron	Intron 1 of 3	Prot: NP_000905.3 UniProt:
	OPRM1 NM_001145279.4		c.569+7817T>G	intron	Intron 3 of 5	Prot: NP_001138751.1 UniProt:
	OPRM1 NM_001285524.1		c.569+7817T>G	intron	Intron 2 of 4	Prot: NP_001272453.1 UniProt:

OPRM1 NM_000914.5

MANE Select

HGVSc / HGVSpc.290+7817T>G

Exon rankIntron 1 of 3

intron

Prot: NP_000905.3UniProt: P35372-1

OPRM1 NM_001145279.4

HGVSc / HGVSpc.569+7817T>G

Exon rankIntron 3 of 5

intron

Prot: NP_001138751.1UniProt: P35372-10

OPRM1 NM_001285524.1

HGVSc / HGVSpc.569+7817T>G

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>G	intron	Intron 1 of 3	Prot: ENSP00000328264.7 UniProt:
	OPRM1 ENST00000434900.6	TSL:1	c.569+7817T>G	intron	Intron 3 of 5	Prot: ENSP00000394624.2 UniProt:
	OPRM1 ENST00000360422.8	TSL:1	c.476+7817T>G	intron	Intron 1 of 3	Prot: ENSP00000353598.5 UniProt:

OPRM1 ENST00000330432.12

TSL:1MANE Select

HGVSc / HGVSpc.290+7817T>G

Exon rankIntron 1 of 3

intron

Prot: ENSP00000328264.7UniProt: P35372-1

OPRM1 ENST00000434900.6

TSL:1

HGVSc / HGVSpc.569+7817T>G

Exon rankIntron 3 of 5

intron

Prot: ENSP00000394624.2UniProt: P35372-10

OPRM1 ENST00000360422.8

TSL:1

HGVSc / HGVSpc.476+7817T>G

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.2
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.67
GPN-Star LLR	N/A	1.7
GPN-Star score	N/A	-1.7
PhyloP100	Benign	-0.28

Showing 7 of 7 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