Genetic Variant ENST00000529564.1:c.284-1791G>A (chr16-31089617-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000529564.1(ENSG00000255439):c.284-1791G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 152,312 control chromosomes in the GnomAD database, including 54 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 0.014 ( 54 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000255439
ENST00000529564.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.561

Publications

3 publications found

Variant links:

Genes affected

ENSG00000255439 (HGNC:):

ENSG00000255439 links:

PRSS53 (HGNC:34407): (serine protease 53) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PRSS53 links:

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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=-0.9).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (2097/152312) while in subpopulation AFR AF = 0.0481 (2000/41556). AF 95% confidence interval is 0.0464. There are 54 homozygotes in GnomAd4. There are 964 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 54 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000255439	ENST00000529564.1 link	c.284-1791G>A	intron_variant	Intron 2 of 4	4	ENSP00000431371.1	E9PLN8
ENSG00000255439	ENST00000533518.5 link	n.*42+1475G>A	intron_variant	Intron 3 of 12	1	ENSP00000433035.1	H0YD56
PRSS53	ENST00000486499.1 link	n.12G>A	non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000255439	ENST00000532364.1 link	c.174-2719G>A	intron_variant	Intron 1 of 1	4	ENSP00000460316.1	I3L3B4

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2092

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0481

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00764

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

230

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

254

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0138

AC:

2097

AN:

152312

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

964

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0481

AC:

2000

AN:

41556

American (AMR)

AF:

0.00392

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68024

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

192

287

383

479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0135

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

9.5

(source)

DANN

Benign

0.70

PhyloP100

0.56

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

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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