dbSNP rs2978974: PSCA:n.139G>A (chr8-142670446-G-A) – 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.139G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,100 control chromosomes in the GnomAD database, including 11,275 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 0.38 ( 11265 hom., cov: 32)

Exomes 𝑓: 0.35 ( 10 hom. )

Consequence

PSCA
ENST00000505305.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

Publications

27 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NR_033343.2 link	n.150G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PSCA	ENST00000505305.1 link	n.139G>A	non_coding_transcript_exon_variant	Exon 1 of 2	3
PSCA	ENST00000510969.1 link	n.126G>A	non_coding_transcript_exon_variant	Exon 1 of 3	2
JRK	ENST00000591357.5 link	n.265-314C>T	intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57157

AN:

151872

Hom.:

11250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.490

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.373

GnomAD4 exome

AF:

0.345

AC:

AN:

110

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

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:

0.372

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.376

AC:

57214

AN:

151990

Hom.:

11265

Cov.:

AF XY:

0.368

AC XY:

27327

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.490

AC:

20288

AN:

41424

American (AMR)

AF:

0.292

AC:

4465

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1054

AN:

3468

East Asian (EAS)

AF:

0.277

AC:

1427

AN:

5156

South Asian (SAS)

AF:

0.290

AC:

1399

AN:

4824

European-Finnish (FIN)

AF:

0.251

AC:

2653

AN:

10574

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.365

AC:

24777

AN:

67950

Other (OTH)

AF:

0.370

AC:

782

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1772

3544

5317

7089

8861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.362

Hom.:

28387

Bravo

AF:

0.383

Asia WGS

AF:

0.287

AC:

1001

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.50

(source)

DANN

Benign

0.72

PhyloP100

-2.1

PromoterAI

-0.21

Neutral

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over