rs1883723

Variant names:

• chr20-1988197-T-C
• rs1883723
• NM_024411.5:c.-20+4387A>G

Variant summary

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

The NM_024411.5(PDYN):​c.-20+4387A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,088 control chromosomes in the GnomAD database, including 1,215 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 0.12 (1215 hom., cov: 32)
• Consequence: PDYN NM_024411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 1 publications found

Genes affected

PDYN (HGNC:8820): (prodynorphin) The protein encoded by this gene is a preproprotein that is proteolytically processed to form the secreted opioid peptides beta-neoendorphin, dynorphin, leu-enkephalin, rimorphin, and leumorphin. These peptides are ligands for the kappa-type of opioid receptor. Dynorphin is involved in modulating responses to several psychoactive substances, including cocaine. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

PDYN-AS1 (HGNC:53462): (PDYN antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDYN	NM_024411.5	c.-20+4387A>G		intron_variant	Intron 2 of 3	ENST00000217305.3	NP_077722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3	c.-20+4387A>G		intron_variant	Intron 2 of 3	1	NM_024411.5	ENSP00000217305.2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18317 AN: 151970 Hom.: 1211 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.121 AC: 18339 AN: 152088 Hom.: 1215 Cov.: 32 AF XY: 0.121 AC XY: 9007 AN XY: 74352

African (AFR) AF: 0.168 AC: 6957 AN: 41448

American (AMR) AF: 0.0807 AC: 1235 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 259 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1029 AN: 5154

South Asian (SAS) AF: 0.136 AC: 652 AN: 4810

European-Finnish (FIN) AF: 0.133 AC: 1404 AN: 10590

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0944 AC: 6420 AN: 68000

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.105 Hom.: 199

Bravo AF: 0.118

Asia WGS AF: 0.225 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.75
PhyloP100		0.0090
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: rs1883723; hg19: chr20-1968843; COSMIC: COSV54102148;