rs4654323

Variant names:

• chr1-28842445-G-T
• rs4654323
• NM_000911.4:c.228-16509G>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.228-16509G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,136 control chromosomes in the GnomAD database, including 6,224 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 0.28 (6224 hom., cov: 32)
• Consequence: OPRD1 NM_000911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.228-16509G>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.228-16509G>T		intron_variant	Intron 1 of 2	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42578 AN: 152018 Hom.: 6224 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.280 AC: 42606 AN: 152136 Hom.: 6224 Cov.: 32 AF XY: 0.281 AC XY: 20859 AN XY: 74360

African (AFR) AF: 0.309 AC: 12808 AN: 41496

American (AMR) AF: 0.321 AC: 4897 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3470

East Asian (EAS) AF: 0.0998 AC: 517 AN: 5178

South Asian (SAS) AF: 0.194 AC: 934 AN: 4822

European-Finnish (FIN) AF: 0.292 AC: 3095 AN: 10584

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18206 AN: 67998

Other (OTH) AF: 0.309 AC: 653 AN: 2112

Alfa AF: 0.277 Hom.: 2115

Bravo AF: 0.288

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.74
PhyloP100		0.30
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: rs4654323; hg19: chr1-29168957;