dbSNP rs2976391: PSCA:c.26-21C>A (chr8-142681306-C-A) – 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.26-21C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,538,732 control chromosomes in the GnomAD database, including 164,741 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 ( 14552 hom., cov: 32)

Exomes 𝑓: 0.46 ( 150189 hom. )

Consequence

PSCA
NM_005672.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

19 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NM_005672.5 link	c.26-21C>A		intron_variant	Intron 1 of 2	ENST00000301258.5	NP_005663.2	O43653D3DWI6
PSCA	NR_033343.2 link	n.273-21C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5 link	c.26-21C>A		intron_variant	Intron 1 of 2	1	NM_005672.5	ENSP00000301258.4		O43653

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66232

AN:

151700

Hom.:

14548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.440

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.445

GnomAD2 exomes

AF:

0.423

AC:

65044

AN:

153664

AF XY:

0.425

show subpopulations

Gnomad AFR exome

AF:

0.402

Gnomad AMR exome

AF:

0.368

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.332

Gnomad FIN exome

AF:

0.436

Gnomad NFE exome

AF:

0.480

Gnomad OTH exome

AF:

0.439

GnomAD4 exome

AF:

0.462

AC:

640295

AN:

1386912

Hom.:

150189

Cov.:

AF XY:

0.459

AC XY:

314253

AN XY:

684370

show subpopulations

African (AFR)

AF:

0.403

AC:

12645

AN:

31366

American (AMR)

AF:

0.375

AC:

13373

AN:

35666

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

10769

AN:

24978

East Asian (EAS)

AF:

0.254

AC:

9043

AN:

35670

South Asian (SAS)

AF:

0.372

AC:

29339

AN:

78886

European-Finnish (FIN)

AF:

0.440

AC:

21378

AN:

48632

Middle Eastern (MID)

AF:

0.449

AC:

2398

AN:

5340

European-Non Finnish (NFE)

AF:

0.482

AC:

515493

AN:

1068876

Other (OTH)

AF:

0.450

AC:

25857

AN:

57498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

16386

32771

49157

65542

81928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.436

AC:

66244

AN:

151820

Hom.:

14552

Cov.:

AF XY:

0.434

AC XY:

32219

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.399

AC:

16532

AN:

41394

American (AMR)

AF:

0.415

AC:

6347

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1456

AN:

3464

East Asian (EAS)

AF:

0.321

AC:

1651

AN:

5146

South Asian (SAS)

AF:

0.382

AC:

1840

AN:

4818

European-Finnish (FIN)

AF:

0.440

AC:

4645

AN:

10546

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.475

AC:

32220

AN:

67862

Other (OTH)

AF:

0.438

AC:

926

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1882

3764

5645

7527

9409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.454

Hom.:

9526

Bravo

AF:

0.433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.77

(source)

DANN

Benign

0.84

PhyloP100

-1.4

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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rs2976391

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