6-154039507-C-T

Variant names:

• chr6-154039507-C-T
• rs9282815
• ENST00000434900.6:c.242C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145279.4(OPRM1):​c.242C>T​(p.Ala81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OPRM1 NM_001145279.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• 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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050633937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145279.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.-38C>T		5_prime_UTR	Exon 1 of 4	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.242C>T	p.Ala81Val	missense	Exon 3 of 6	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.242C>T	p.Ala81Val	missense	Exon 2 of 5	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.242C>T	p.Ala81Val	missense	Exon 3 of 6	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.149C>T	p.Ala50Val	missense	Exon 1 of 4	ENSP00000353598.5	L0E130
	OPRM1	ENST00000520282.5	TSL:1	c.107C>T	p.Ala36Val	missense	Exon 2 of 3	ENSP00000430247.1	E7EW71

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000101 AC: 2 AN: 198824 AF XY: 0.00000936

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1430750 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708690

African (AFR) AF: 0.00 AC: 0 AN: 32894

American (AMR) AF: 0.00 AC: 0 AN: 39692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 38128

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096508

Other (OTH) AF: 0.00 AC: 0 AN: 59218

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000832 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.8
DANN	Benign	0.91
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.18
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.024
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.059
MutPred		0.26		Loss of sheet (P = 0.0025)
MVP		0.048
MPC		0.049
ClinPred		0.35	T
GERP RS		-9.3
PromoterAI		-0.0074	Neutral
gMVP		0.20
Mutation Taster		=298/2	polymorphism

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

Other links and lift over

dbSNP: rs9282815; hg19: chr6-154360642;