Genetic Variant PDYN-AS1:n.1217-11566T>C (chr20-1995366-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000446562.1(PDYN-AS1):n.1217-11566T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0059 ( 9 hom., cov: 16)

Failed GnomAD Quality Control

Consequence

PDYN-AS1
ENST00000446562.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.48

Publications

3 publications found

Variant links:

Genes affected

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

PDYN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDYN-AS1	NR_134520.1 link	n.1253-11566T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDYN-AS1	ENST00000446562.1 link	n.1217-11566T>C		intron_variant	Intron 3 of 3	2
PDYN-AS1	ENST00000651021.1 link	n.475+29023T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00585

AC:

455

AN:

77780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00355

Gnomad ASJ

AF:

0.00282

Gnomad EAS

AF:

0.0470

Gnomad SAS

AF:

0.00818

Gnomad FIN

AF:

0.00281

Gnomad MID

AF:

0.00581

Gnomad NFE

AF:

0.00371

Gnomad OTH

AF:

0.00439

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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00587

AC:

457

AN:

77834

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

232

AN XY:

37134

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0111

AC:

238

AN:

21346

American (AMR)

AF:

0.00355

AC:

AN:

7896

Ashkenazi Jewish (ASJ)

AF:

0.00282

AC:

AN:

2128

East Asian (EAS)

AF:

0.0470

AC:

AN:

234

South Asian (SAS)

AF:

0.00821

AC:

AN:

1218

European-Finnish (FIN)

AF:

0.00281

AC:

AN:

4986

Middle Eastern (MID)

AF:

0.00625

AC:

AN:

160

European-Non Finnish (NFE)

AF:

0.00374

AC:

143

AN:

38278

Other (OTH)

AF:

0.00529

AC:

AN:

1134

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.357

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.289

Hom.:

548

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.21

(source)

DANN

Benign

0.57

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over