6-154128968-A-T

Position:

• chr6-154128968-A-T

Variant summary

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

The NM_000914.5(OPRM1):​c.*10247A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,030 control chromosomes in the GnomAD database, including 33,997 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 0.67 (33997 hom., cov: 32)
• Consequence: OPRM1 NM_000914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5	c.*10247A>T		3_prime_UTR_variant	4/4	ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12	c.*10247A>T		3_prime_UTR_variant	4/4	1	NM_000914.5	ENSP00000328264	P1
OPRM1	ENST00000337049.8	c.1164+37496A>T		intron_variant		1		ENSP00000338381
OPRM1	ENST00000524150.2	c.*250+37496A>T		intron_variant, NMD_transcript_variant		5		ENSP00000430575

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101115 AN: 151912 Hom.: 33988 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.665 AC: 101161 AN: 152030 Hom.: 33997 Cov.: 32 AF XY: 0.672 AC XY: 49908 AN XY: 74310

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.705

Alfa AF: 0.553 Hom.: 1673

Bravo AF: 0.669

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.040
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: rs678122; hg19: chr6-154450103;