rs2976391

Positions:

• chr8-142681306-C-A
• chr8-142681306-C-G
• chr8-142681306-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PSCA	NM_005672.5	c.26-21C>A		intron_variant		ENST00000301258.5	NP_005663.2
PSCA	NR_033343.2	n.273-21C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5	c.26-21C>A		intron_variant		1	NM_005672.5	ENSP00000301258.4

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66232 AN: 151700 Hom.: 14548 Cov.: 32

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

GnomAD3 exomes AF: 0.423 AC: 65044 AN: 153664 Hom.: 14006 AF XY: 0.425 AC XY: 34668 AN XY: 81580

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 SAS exome AF: 0.371

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.: 27 AF XY: 0.459 AC XY: 314253 AN XY: 684370

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.450

GnomAD4 genome AF: 0.436 AC: 66244 AN: 151820 Hom.: 14552 Cov.: 32 AF XY: 0.434 AC XY: 32219 AN XY: 74198

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.438

Alfa AF: 0.453 Hom.: 8158

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
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs2976391; hg19: chr8-143762724; COSMIC: COSV56652616;