dbSNP rs1997794: PDYN:c.-321A>G (chr20-1994212-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001190899.2(PDYN):c.-321A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 153,520 control chromosomes in the GnomAD database, including 21,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 21323 hom., cov: 31)

Exomes 𝑓: 0.40 ( 153 hom. )

Consequence

PDYN
NM_001190899.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0800

Publications

36 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 20-1994212-T-C is Benign according to our data. Variant chr20-1994212-T-C is described in ClinVar as Benign. ClinVar VariationId is 337846.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDYN	NM_001190899.2		c.-321A>G	5_prime_UTR	Exon 1 of 3	NP_001177828.1	P01213
PDYN-AS1	NR_134520.1		n.1253-12720T>C	intron	N/A
PDYN	NM_024411.5	MANE Select	c.-381A>G	upstream_gene	N/A	NP_077722.1	P01213

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDYN	ENST00000539905.5	TSL:4	c.-321A>G	5_prime_UTR	Exon 1 of 3	ENSP00000440185.1	P01213
PDYN	ENST00000651882.1		c.-378A>G	5_prime_UTR	Exon 1 of 4	ENSP00000498752.1	A0A494C0X3
PDYN-AS1	ENST00000446562.1	TSL:2	n.1217-12720T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75751

AN:

151842

Hom.:

21280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.402

AC:

627

AN:

1560

Hom.:

153

Cov.:

AF XY:

0.396

AC XY:

343

AN XY:

866

show subpopulations

African (AFR)

AF:

0.722

AC:

AN:

American (AMR)

AF:

0.450

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

AN:

East Asian (EAS)

AF:

0.803

AC:

143

AN:

178

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

210

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.338

AC:

338

AN:

1000

Other (OTH)

AF:

0.409

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.499

AC:

75857

AN:

151960

Hom.:

21323

Cov.:

AF XY:

0.502

AC XY:

37275

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.750

AC:

31093

AN:

41438

American (AMR)

AF:

0.418

AC:

6389

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1199

AN:

3470

East Asian (EAS)

AF:

0.852

AC:

4388

AN:

5152

South Asian (SAS)

AF:

0.576

AC:

2768

AN:

4808

European-Finnish (FIN)

AF:

0.384

AC:

4058

AN:

10556

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24528

AN:

67948

Other (OTH)

AF:

0.461

AC:

973

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1725

3449

5174

6898

8623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.414

Hom.:

21329

Bravo

AF:

0.512

Asia WGS

AF:

0.753

AC:

2617

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant cerebellar ataxia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

-0.080

PromoterAI

-0.080

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over