chr6-154107531-C-T

Variant names:

• chr6-154107531-C-T
• rs677830
• ENST00000419506.6:c.1231C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001145286.3(OPRM1):​c.1231C>T​(p.Gln411*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 718,426 control chromosomes in the GnomAD database, including 17,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3490 hom., cov: 32)
  • Exomes 𝑓: 0.22 (14070 hom.)
• Consequence: OPRM1 NM_001145286.3 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.685
• Publications: 27 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-154107531-C-T is Benign according to our data. Variant chr6-154107531-C-T is described in ClinVar as Benign. ClinVar VariationId is 403268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145286.3. 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.1165-11152C>T		intron	N/A	NP_000905.3
	OPRM1	NM_001145286.3		c.1231C>T	p.Gln411*	stop_gained	Exon 4 of 4	NP_001138758.1
	OPRM1	NM_001145279.4		c.1444-11152C>T		intron	N/A	NP_001138751.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000419506.6	TSL:1	c.1231C>T	p.Gln411*	stop_gained	Exon 4 of 4	ENSP00000403549.2
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.1165-11152C>T		intron	N/A	ENSP00000328264.7
	OPRM1	ENST00000434900.6	TSL:1	c.1444-11152C>T		intron	N/A	ENSP00000394624.2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31411 AN: 152066 Hom.: 3487 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.195 AC: 29485 AN: 151582 AF XY: 0.196

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0964

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.216 AC: 122057 AN: 566240 Hom.: 14070 Cov.: 0 AF XY: 0.215 AC XY: 65748 AN XY: 305474

African (AFR) AF: 0.166 AC: 2624 AN: 15812

American (AMR) AF: 0.152 AC: 5278 AN: 34718

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 4064 AN: 20030

East Asian (EAS) AF: 0.0860 AC: 2760 AN: 32106

South Asian (SAS) AF: 0.160 AC: 10071 AN: 62774

European-Finnish (FIN) AF: 0.199 AC: 9733 AN: 48960

Middle Eastern (MID) AF: 0.286 AC: 1165 AN: 4078

European-Non Finnish (NFE) AF: 0.251 AC: 79708 AN: 317060

Other (OTH) AF: 0.217 AC: 6654 AN: 30702

GnomAD4 genome AF: 0.207 AC: 31444 AN: 152186 Hom.: 3490 Cov.: 32 AF XY: 0.201 AC XY: 14973 AN XY: 74422

African (AFR) AF: 0.168 AC: 6976 AN: 41510

American (AMR) AF: 0.189 AC: 2895 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3470

East Asian (EAS) AF: 0.0846 AC: 438 AN: 5180

South Asian (SAS) AF: 0.145 AC: 701 AN: 4830

European-Finnish (FIN) AF: 0.189 AC: 1995 AN: 10582

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17037 AN: 68004

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.227 Hom.: 7429

Bravo AF: 0.204

TwinsUK AF: 0.262 AC: 971

ALSPAC AF: 0.249 AC: 958

ExAC AF: 0.179 AC: 3917

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.90	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.80
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0017	N
PhyloP100		-0.69
Vest4		0.086
GERP RS		0.23
Mutation Taster		=190/10	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs677830; hg19: chr6-154428666; COSMIC: COSV57822668;