chr6-154108891-A-G

Variant names:

• chr6-154108891-A-G
• rs623956
• ENST00000414028.6:c.*1096A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000414028.6(OPRM1):​c.*1096A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 984,140 control chromosomes in the GnomAD database, including 29,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (3484 hom., cov: 32)
  • Exomes 𝑓: 0.25 (26036 hom.)
• Consequence: OPRM1 ENST00000414028.6 3_prime_UTR
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.184
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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: ENST00000414028.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	NM_000914.5	MANE Select	c.1165-9792A>G		intron	N/A	NP_000905.3
	OPRM1	NR_104351.1		n.2551A>G		non_coding_transcript_exon	Exon 5 of 5
	OPRM1	NM_001145284.3		c.*1096A>G		3_prime_UTR	Exon 4 of 4	NP_001138756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000414028.6	TSL:1	c.*1096A>G		3_prime_UTR	Exon 4 of 4	ENSP00000399359.2
	OPRM1	ENST00000435918.6	TSL:1	c.*846A>G		3_prime_UTR	Exon 4 of 4	ENSP00000413752.2
	OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.1165-9792A>G		intron	N/A	ENSP00000328264.7

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31407 AN: 152048 Hom.: 3481 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: 0.145

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.248 AC: 206463 AN: 831974 Hom.: 26036 Cov.: 23 AF XY: 0.248 AC XY: 95381 AN XY: 384268

African (AFR) AF: 0.157 AC: 2467 AN: 15762

American (AMR) AF: 0.169 AC: 166 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 1016 AN: 5146

East Asian (EAS) AF: 0.0958 AC: 347 AN: 3622

South Asian (SAS) AF: 0.150 AC: 2474 AN: 16444

European-Finnish (FIN) AF: 0.225 AC: 62 AN: 276

Middle Eastern (MID) AF: 0.244 AC: 395 AN: 1620

European-Non Finnish (NFE) AF: 0.254 AC: 193253 AN: 760858

Other (OTH) AF: 0.230 AC: 6283 AN: 27262

GnomAD4 genome AF: 0.207 AC: 31440 AN: 152166 Hom.: 3484 Cov.: 32 AF XY: 0.201 AC XY: 14966 AN XY: 74402

African (AFR) AF: 0.168 AC: 6975 AN: 41504

American (AMR) AF: 0.189 AC: 2893 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3468

East Asian (EAS) AF: 0.0847 AC: 439 AN: 5186

South Asian (SAS) AF: 0.146 AC: 702 AN: 4818

European-Finnish (FIN) AF: 0.188 AC: 1997 AN: 10600

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

European-Non Finnish (NFE) AF: 0.251 AC: 17033 AN: 67978

Other (OTH) AF: 0.192 AC: 406 AN: 2112

Alfa AF: 0.230 Hom.: 555

Bravo AF: 0.204

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.50
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs623956; hg19: chr6-154430026;