Genetic Variant PENK-AS1:n.694+1426T>C (chr8-56447926-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000518662.5(PENK-AS1):n.694+1426T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,120 control chromosomes in the GnomAD database, including 11,075 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 0.35 ( 11075 hom., cov: 32)

Consequence

PENK-AS1
ENST00000518662.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.179

Publications

14 publications found

Variant links:

Genes affected

PENK-AS1 (HGNC:55519): (PENK antisense RNA 1)

PENK-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PENK-AS1	NR_125813.1 link	n.694+1426T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PENK-AS1	ENST00000518662.5 link	n.694+1426T>C	intron_variant	Intron 1 of 3	2
PENK-AS1	ENST00000662661.1 link	n.264+1426T>C	intron_variant	Intron 1 of 4
PENK-AS1	ENST00000685796.1 link	n.657+1426T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53137

AN:

152002

Hom.:

11072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.366

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

GnomAD4 genome

AF:

0.349

AC:

53148

AN:

152120

Hom.:

11075

Cov.:

AF XY:

0.353

AC XY:

26228

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.116

AC:

4838

AN:

41536

American (AMR)

AF:

0.344

AC:

5267

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

1704

AN:

3470

East Asian (EAS)

AF:

0.352

AC:

1817

AN:

5164

South Asian (SAS)

AF:

0.469

AC:

2259

AN:

4816

European-Finnish (FIN)

AF:

0.535

AC:

5653

AN:

10570

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30330

AN:

67956

Other (OTH)

AF:

0.366

AC:

770

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1652

3303

4955

6606

8258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.405

Hom.:

18810

Bravo

AF:

0.324

Asia WGS

AF:

0.406

AC:

1413

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.5

(source)

DANN

Benign

0.52

PhyloP100

0.18

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over