chr1-28843047-T-C

Variant names:

• chr1-28843047-T-C
• rs3766951
• NM_000911.4:c.228-15907T>C

Variant summary

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

The NM_000911.4(OPRD1):​c.228-15907T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,642 control chromosomes in the GnomAD database, including 9,378 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 0.35 (9378 hom., cov: 31)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 18 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.228-15907T>C		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.228-15907T>C		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52593 AN: 151538 Hom.: 9373 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.347 AC: 52632 AN: 151642 Hom.: 9378 Cov.: 31 AF XY: 0.345 AC XY: 25526 AN XY: 74050

African (AFR) AF: 0.400 AC: 16516 AN: 41330

American (AMR) AF: 0.366 AC: 5567 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3468

East Asian (EAS) AF: 0.188 AC: 970 AN: 5170

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4804

European-Finnish (FIN) AF: 0.316 AC: 3302 AN: 10434

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22518 AN: 67908

Other (OTH) AF: 0.380 AC: 799 AN: 2102

Alfa AF: 0.348 Hom.: 12858

Bravo AF: 0.357

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.29
PhyloP100		-0.84
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: rs3766951; hg19: chr1-29169559;