rs6045824

Positions:

• chr20-1981331-T-C

Variant summary

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

The NM_024411.5(PDYN):​c.130-373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,038 control chromosomes in the GnomAD database, including 1,799 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 0.14 (1799 hom., cov: 32)
• Consequence: PDYN NM_024411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDYN	NM_024411.5	c.130-373A>G		intron_variant		ENST00000217305.3	NP_077722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3	c.130-373A>G		intron_variant		1	NM_024411.5	ENSP00000217305.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21286 AN: 151920 Hom.: 1791 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.140 AC: 21332 AN: 152038 Hom.: 1799 Cov.: 32 AF XY: 0.135 AC XY: 10050 AN XY: 74314

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.160

Alfa AF: 0.118 Hom.: 552

Bravo AF: 0.148

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6045824; hg19: chr20-1961977;