rs6045868

Variant names:

• chr20-1986632-G-A
• rs6045868
• NM_024411.5:c.-19-3529C>T

Variant summary

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

The NM_024411.5(PDYN):​c.-19-3529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,022 control chromosomes in the GnomAD database, including 13,176 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 0.38 (13176 hom., cov: 32)
• Consequence: PDYN NM_024411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDYN	NM_024411.5	c.-19-3529C>T		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.-19-3529C>T		intron_variant	Intron 2 of 3	1	NM_024411.5	ENSP00000217305.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58211 AN: 151904 Hom.: 13137 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.384 AC: 58304 AN: 152022 Hom.: 13176 Cov.: 32 AF XY: 0.383 AC XY: 28498 AN XY: 74330

African (AFR) AF: 0.621 AC: 25730 AN: 41440

American (AMR) AF: 0.336 AC: 5130 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3472

East Asian (EAS) AF: 0.628 AC: 3233 AN: 5150

South Asian (SAS) AF: 0.410 AC: 1974 AN: 4810

European-Finnish (FIN) AF: 0.238 AC: 2512 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17661 AN: 67980

Other (OTH) AF: 0.367 AC: 776 AN: 2112

Alfa AF: 0.300 Hom.: 12815

Bravo AF: 0.403

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.069
DANN	Benign	0.42
PhyloP100		-1.8
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: rs6045868; hg19: chr20-1967278;