1-28818676-C-T

Variant names:

• chr1-28818676-C-T
• rs678849
• NM_000911.4:c.227+6066C>T

Variant summary

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

The NM_000911.4(OPRD1):​c.227+6066C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,982 control chromosomes in the GnomAD database, including 16,678 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 0.45 (16678 hom., cov: 31)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 58 publications found

Genes affected

OPRD1 (HGNC:8153): (opioid receptor delta 1) Enables G protein-coupled enkephalin receptor activity. Involved in several processes, including G protein-coupled opioid receptor signaling pathway; cellular response to hypoxia; and positive regulation of peptidyl-serine phosphorylation. Is intrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305996 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.227+6066C>T		intron_variant	Intron 1 of 2	ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7	c.227+6066C>T		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2
ENSG00000305996	ENST00000814652.1	n.92-9247C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68103 AN: 151864 Hom.: 16681 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.448 AC: 68118 AN: 151982 Hom.: 16678 Cov.: 31 AF XY: 0.449 AC XY: 33354 AN XY: 74312

African (AFR) AF: 0.249 AC: 10316 AN: 41450

American (AMR) AF: 0.386 AC: 5898 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3137 AN: 5154

South Asian (SAS) AF: 0.639 AC: 3079 AN: 4818

European-Finnish (FIN) AF: 0.536 AC: 5668 AN: 10572

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36665 AN: 67948

Other (OTH) AF: 0.420 AC: 886 AN: 2110

Alfa AF: 0.492 Hom.: 39885

Bravo AF: 0.422

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.030
DANN	Benign	0.74
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs678849; hg19: chr1-29145188; COSMIC: COSV52380936;