dbSNP rs2920297: PSCA:c.133+231A>G (chr8-142681665-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005672.5(PSCA):c.133+231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 609,096 control chromosomes in the GnomAD database, including 65,065 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 ( 14944 hom., cov: 31)

Exomes 𝑓: 0.46 ( 50121 hom. )

Consequence

PSCA
NM_005672.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.30

Publications

10 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=-1.01).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NM_005672.5 link	c.133+231A>G		intron_variant	Intron 2 of 2	ENST00000301258.5	NP_005663.2	O43653D3DWI6
PSCA	NR_033343.2 link	n.380+231A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5 link	c.133+231A>G		intron_variant	Intron 2 of 2	1	NM_005672.5	ENSP00000301258.4		O43653

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

66953

AN:

151304

Hom.:

14917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.442

GnomAD4 exome

AF:

0.464

AC:

212230

AN:

457674

Hom.:

50121

Cov.:

AF XY:

0.462

AC XY:

111310

AN XY:

240714

show subpopulations

African (AFR)

AF:

0.388

AC:

5013

AN:

12918

American (AMR)

AF:

0.541

AC:

11683

AN:

21578

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

7114

AN:

14068

East Asian (EAS)

AF:

0.516

AC:

16020

AN:

31034

South Asian (SAS)

AF:

0.449

AC:

21264

AN:

47410

European-Finnish (FIN)

AF:

0.504

AC:

15081

AN:

29922

Middle Eastern (MID)

AF:

0.479

AC:

1224

AN:

2556

European-Non Finnish (NFE)

AF:

0.452

AC:

122832

AN:

271784

Other (OTH)

AF:

0.454

AC:

11999

AN:

26404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

5651

11302

16954

22605

28256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.443

AC:

67019

AN:

151422

Hom.:

14944

Cov.:

AF XY:

0.443

AC XY:

32802

AN XY:

73970

show subpopulations

African (AFR)

AF:

0.390

AC:

16085

AN:

41206

American (AMR)

AF:

0.511

AC:

7794

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1790

AN:

3460

East Asian (EAS)

AF:

0.352

AC:

1800

AN:

5114

South Asian (SAS)

AF:

0.414

AC:

1985

AN:

4790

European-Finnish (FIN)

AF:

0.510

AC:

5356

AN:

10508

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.454

AC:

30787

AN:

67806

Other (OTH)

AF:

0.444

AC:

931

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1913

3826

5738

7651

9564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.453

Hom.:

8204

Bravo

AF:

0.439

Asia WGS

AF:

0.402

AC:

1397

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.40

(source)

DANN

Benign

0.22

PhyloP100

-5.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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rs2920297

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over