chr20-1986632-G-A

Position:

• chr20-1986632-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000217305.3(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 ENST00000217305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PDYN	NM_024411.5	c.-19-3529C>T		intron_variant		ENST00000217305.3	NP_077722.1
PDYN-AS1	NR_134520.1	n.1252+20289G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3	c.-19-3529C>T		intron_variant		1	NM_024411.5	ENSP00000217305	P1
PDYN-AS1	ENST00000651021.1	n.475+20289G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.367

Alfa AF: 0.291 Hom.: 9350

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6045868; hg19: chr20-1967278;