dbSNP rs9297976: PSCA:n.261+249T>C (chr8-142670817-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+249T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,068 control chromosomes in the GnomAD database, including 12,944 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 0.41 ( 12944 hom., cov: 32)

Consequence

PSCA
ENST00000505305.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

15 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NR_033343.2 link	n.272+249T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PSCA	ENST00000505305.1 link	n.261+249T>C	intron_variant	Intron 1 of 1	3
PSCA	ENST00000510969.1 link	n.248+249T>C	intron_variant	Intron 1 of 2	2
JRK	ENST00000591357.5 link	n.265-685A>G	intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62520

AN:

151952

Hom.:

12940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.427

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

GnomAD4 genome

AF:

0.411

AC:

62543

AN:

152068

Hom.:

12944

Cov.:

AF XY:

0.408

AC XY:

30293

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.414

AC:

17187

AN:

41468

American (AMR)

AF:

0.387

AC:

5922

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1353

AN:

3470

East Asian (EAS)

AF:

0.322

AC:

1662

AN:

5162

South Asian (SAS)

AF:

0.350

AC:

1687

AN:

4816

European-Finnish (FIN)

AF:

0.405

AC:

4278

AN:

10566

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29018

AN:

67980

Other (OTH)

AF:

0.421

AC:

888

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1926

3853

5779

7706

9632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.343

Hom.:

2191

Bravo

AF:

0.412

Asia WGS

AF:

0.303

AC:

1063

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.49

(source)

DANN

Benign

0.61

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