Variant 20-1979667-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024411.5(PDYN):c.*656T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 157,242 control chromosomes in the GnomAD database, including 1,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1176 hom., cov: 31)

Exomes 𝑓: 0.081 ( 20 hom. )

Consequence

PDYN
NM_024411.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.664

Variant links:

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 links:

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

PDYN-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-1979667-A-G is Benign according to our data. Variant chr20-1979667-A-G is described in ClinVar as [Benign]. Clinvar id is 337822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDYN	NM_024411.5 linkuse as main transcript	c.*656T>C		3_prime_UTR_variant	4/4	ENST00000217305.3	NP_077722.1
PDYN-AS1	NR_134520.1 linkuse as main transcript	n.1252+13324A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3 linkuse as main transcript	c.*656T>C		3_prime_UTR_variant	4/4	1	NM_024411.5	ENSP00000217305	P1
PDYN-AS1	ENST00000651021.1 linkuse as main transcript	n.475+13324A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18036

AN:

152032

Hom.:

1174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0598

Gnomad FIN

AF:

0.0813

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.0805

AC:

410

AN:

5092

Hom.:

Cov.:

AF XY:

0.0805

AC XY:

216

AN XY:

2684

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.0619

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0389

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.0989

Gnomad4 OTH exome

AF:

0.0875

GnomAD4 genome

AF:

0.119

AC:

18057

AN:

152150

Hom.:

1176

Cov.:

AF XY:

0.115

AC XY:

8582

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.0998

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0609

Gnomad4 FIN

AF:

0.0813

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.120

Hom.:

888

Bravo

AF:

0.124

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.2

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over