rs9478498

Variant names:

• chr6-154020241-C-T
• rs9478498
• ENST00000434900.6:c.-1+9223C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145279.4(OPRM1):​c.-1+9223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,002 control chromosomes in the GnomAD database, including 8,282 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 0.31 (8282 hom., cov: 32)
• Consequence: OPRM1 NM_001145279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_001145279.4	c.-1+9223C>T		intron_variant	Intron 1 of 5		NP_001138751.1
OPRM1	NM_001145281.3	c.47+9682C>T		intron_variant	Intron 1 of 3		NP_001138753.1
OPRM1	NM_001145280.4	c.-11+9223C>T		intron_variant	Intron 1 of 3		NP_001138752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000434900.6	c.-1+9223C>T		intron_variant	Intron 1 of 5	1		ENSP00000394624.2
OPRM1	ENST00000518759.5	c.47+9682C>T		intron_variant	Intron 1 of 3	1		ENSP00000430260.1
OPRM1	ENST00000520708.5	c.-11+9223C>T		intron_variant	Intron 1 of 3	1		ENSP00000430876.1
OPRM1	ENST00000520282.5	c.10+9223C>T		intron_variant	Intron 1 of 2	1		ENSP00000430247.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47457 AN: 151884 Hom.: 8250 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.313 AC: 47543 AN: 152002 Hom.: 8282 Cov.: 32 AF XY: 0.307 AC XY: 22826 AN XY: 74310

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.294

Alfa AF: 0.289 Hom.: 1613

Bravo AF: 0.326

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9478498; hg19: chr6-154341376;