rs9371776

chr6-154120430-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000914.5(OPRM1):c.*1709G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 152,184 control chromosomes in the GnomAD database, including 7 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 0.0035 (7 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00346 (526/152184) while in subpopulation EAS AF= 0.0458 (237/5178). AF 95% confidence interval is 0.041. There are 7 homozygotes in gnomad4. There are 287 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5	c.*1709G>A		3_prime_UTR_variant	4/4	ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12	c.*1709G>A		3_prime_UTR_variant	4/4	1	NM_000914.5	P1
OPRM1	ENST00000337049.8	c.1164+28958G>A		intron_variant		1
OPRM1	ENST00000524150.2	c.*250+28958G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 529 AN: 152066 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00430

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

GnomAD4 genome AF: 0.00346 AC: 526 AN: 152184 Hom.: 7 Cov.: 32 AF XY: 0.00386 AC XY: 287 AN XY: 74434

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0458

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00222 Hom.: 1

Bravo AF: 0.00570

Asia WGS AF: 0.0190 AC: 67 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.50
Dann	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9371776; hg19: chr6-154441565;