chr1-28868389-C-T

Variant names:

• chr1-28868389-C-T
• rs1485471
• NM_000911.4:c.*5106C>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.*5106C>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 0.265 in 152,226 control chromosomes in the GnomAD database, including 6,716 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 0.26 (6716 hom., cov: 33)
  • Exomes 𝑓: 0.29 (0 hom.)
• Consequence: OPRD1 NM_000911.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.*5106C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7	c.*5106C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40254 AN: 152094 Hom.: 6712 Cov.: 33

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.286 AC: 4 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AF: 0.250 AC: 1 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000388202), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.265 AC: 40266 AN: 152212 Hom.: 6716 Cov.: 33 AF XY: 0.271 AC XY: 20185 AN XY: 74416

African (AFR) AF: 0.0719 AC: 2987 AN: 41566

American (AMR) AF: 0.314 AC: 4803 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3470

East Asian (EAS) AF: 0.0701 AC: 363 AN: 5182

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4830

European-Finnish (FIN) AF: 0.435 AC: 4594 AN: 10562

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24220 AN: 67998

Other (OTH) AF: 0.261 AC: 551 AN: 2114

Alfa AF: 0.314 Hom.: 20056

Bravo AF: 0.242

Asia WGS AF: 0.183 AC: 638 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	0.47
DANN	Benign	0.57
PhyloP100		-1.1

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: rs1485471; hg19: chr1-29194901;