chr20-1980488-A-G

Variant names:

• chr20-1980488-A-G
• rs6045819
• NM_024411.5:c.600T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024411.5(PDYN):​c.600T>C​(p.His200His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,502 control chromosomes in the GnomAD database, including 13,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2318 hom., cov: 31)
  • Exomes 𝑓: 0.12 (11033 hom.)
• Consequence: PDYN NM_024411.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.93
• Publications: 22 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-1980488-A-G is Benign according to our data. Variant chr20-1980488-A-G is described in ClinVar as Benign. ClinVar VariationId is 337834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024411.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	NM_024411.5	MANE Select	c.600T>C	p.His200His	synonymous	Exon 4 of 4	NP_077722.1	P01213
	PDYN	NM_001190892.1		c.600T>C	p.His200His	synonymous	Exon 3 of 3	NP_001177821.1	P01213
	PDYN	NM_001190898.3		c.600T>C	p.His200His	synonymous	Exon 4 of 4	NP_001177827.1	P01213

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	ENST00000217305.3	TSL:1 MANE Select	c.600T>C	p.His200His	synonymous	Exon 4 of 4	ENSP00000217305.2	P01213
	PDYN	ENST00000539905.5	TSL:4	c.600T>C	p.His200His	synonymous	Exon 3 of 3	ENSP00000440185.1	P01213
	PDYN	ENST00000540134.5	TSL:4	c.600T>C	p.His200His	synonymous	Exon 4 of 4	ENSP00000442259.1	P01213

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23448 AN: 151562 Hom.: 2312 Cov.: 31

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.106 AC: 26563 AN: 251350 AF XY: 0.103

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.0784

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0795

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.115 AC: 168373 AN: 1461820 Hom.: 11033 Cov.: 33 AF XY: 0.114 AC XY: 82707 AN XY: 727216

African (AFR) AF: 0.291 AC: 9749 AN: 33476

American (AMR) AF: 0.0832 AC: 3719 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3039 AN: 26136

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.0693 AC: 5978 AN: 86252

European-Finnish (FIN) AF: 0.0814 AC: 4351 AN: 53420

Middle Eastern (MID) AF: 0.188 AC: 1085 AN: 5768

European-Non Finnish (NFE) AF: 0.120 AC: 133207 AN: 1111950

Other (OTH) AF: 0.120 AC: 7237 AN: 60396

GnomAD4 genome AF: 0.155 AC: 23480 AN: 151682 Hom.: 2318 Cov.: 31 AF XY: 0.151 AC XY: 11159 AN XY: 74098

African (AFR) AF: 0.279 AC: 11523 AN: 41308

American (AMR) AF: 0.122 AC: 1864 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3468

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5136

South Asian (SAS) AF: 0.0638 AC: 306 AN: 4796

European-Finnish (FIN) AF: 0.0799 AC: 842 AN: 10540

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8003 AN: 67874

Other (OTH) AF: 0.174 AC: 367 AN: 2108

Alfa AF: 0.131 Hom.: 2810

Bravo AF: 0.165

Asia WGS AF: 0.0500 AC: 175 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.129

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Spinocerebellar ataxia type 23 (4)
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.012
DANN	Benign	0.36
PhyloP100		-2.9
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: rs6045819; hg19: chr20-1961134; COSMIC: COSV54103447;