chr6-154056606-C-T

Position:

• chr6-154056606-C-T

Variant summary

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

The NM_000914.5(OPRM1):​c.290+16772C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 151,528 control chromosomes in the GnomAD database, including 346 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 0.053 (346 hom., cov: 31)
• Consequence: OPRM1 NM_000914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.290+16772C>T		intron_variant		ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.290+16772C>T		intron_variant		1	NM_000914.5	ENSP00000328264	P1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8077 AN: 151410 Hom.: 338 Cov.: 31

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.0818

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

GnomAD4 genome AF: 0.0534 AC: 8093 AN: 151528 Hom.: 346 Cov.: 31 AF XY: 0.0534 AC XY: 3954 AN XY: 74008

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0850

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0343

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0505 Hom.: 56

Bravo AF: 0.0643

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs476685; hg19: chr6-154377741;