Genetic Variant PSCA:n.261+5051T>C (chr8-142675619-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 ENST00000505305.1(PSCA):n.261+5051T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,122 control chromosomes in the GnomAD database, including 15,075 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 0.44 ( 15075 hom., cov: 33)

Consequence

PSCA
ENST00000505305.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

22 publications found

Variant links:

Genes affected

PSCA (HGNC:9500): (prostate stem cell antigen) This gene encodes a glycosylphosphatidylinositol-anchored cell membrane glycoprotein. In addition to being highly expressed in the prostate it is also expressed in the bladder, placenta, colon, kidney, and stomach. This gene is up-regulated in a large proportion of prostate cancers and is also detected in cancers of the bladder and pancreas. This gene includes a polymorphism that results in an upstream start codon in some individuals; this polymorphism is thought to be associated with a risk for certain gastric and bladder cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

PSCA links:

JRK (HGNC:6199): (Jrk helix-turn-helix protein) This gene encodes a conserved protein that is similar to DNA-binding proteins, such as major centromere autoantigen B (CENPB). Inactivation of the related gene in mice resulted in epileptic seizures. Childhood Absence Epilepsy (CAE) has been mapped to the same chromosomal location (8q24.3) as this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

JRK 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=-0.99).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NR_033343.2 link	n.272+5051T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PSCA	ENST00000505305.1 link	n.261+5051T>C	intron_variant	Intron 1 of 1	3
PSCA	ENST00000510969.1 link	n.248+5051T>C	intron_variant	Intron 1 of 2	2
JRK	ENST00000591357.5 link	n.265-5487A>G	intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67174

AN:

152004

Hom.:

15042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.442

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

GnomAD4 genome

AF:

0.442

AC:

67249

AN:

152122

Hom.:

15075

Cov.:

AF XY:

0.443

AC XY:

32979

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.389

AC:

16153

AN:

41488

American (AMR)

AF:

0.512

AC:

7836

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1792

AN:

3464

East Asian (EAS)

AF:

0.351

AC:

1817

AN:

5170

South Asian (SAS)

AF:

0.412

AC:

1988

AN:

4826

European-Finnish (FIN)

AF:

0.508

AC:

5380

AN:

10592

Middle Eastern (MID)

AF:

0.476

AC:

139

AN:

292

European-Non Finnish (NFE)

AF:

0.454

AC:

30852

AN:

67966

Other (OTH)

AF:

0.444

AC:

938

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1970

3940

5911

7881

9851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.452

Hom.:

17792

Bravo

AF:

0.439

Asia WGS

AF:

0.405

AC:

1404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.3

(source)

DANN

Benign

0.66

PhyloP100

-1.3

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