rs2976392

Positions:

• chr8-142681514-G-A
• chr8-142681514-G-T

Variant summary

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

The NM_005672.5(PSCA):​c.133+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,296,764 control chromosomes in the GnomAD database, including 134,274 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 0.45 (15416 hom., cov: 32)
  • Exomes 𝑓: 0.45 (118858 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSCA	NM_005672.5	c.133+80G>A		intron_variant		ENST00000301258.5	NP_005663.2
PSCA	NR_033343.2	n.380+80G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000301258.5	c.133+80G>A		intron_variant		1	NM_005672.5	ENSP00000301258.4

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68087 AN: 151782 Hom.: 15383 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.447

GnomAD3 exomes AF: 0.463 AC: 66033 AN: 142688 Hom.: 15620 AF XY: 0.460 AC XY: 35259 AN XY: 76684

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.303

Gnomad SAS exome AF: 0.447

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.448

Gnomad OTH exome AF: 0.473

GnomAD4 exome AF: 0.450 AC: 514940 AN: 1144862 Hom.: 118858 Cov.: 15 AF XY: 0.450 AC XY: 258545 AN XY: 574178

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.506

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.449 AC: 68162 AN: 151902 Hom.: 15416 Cov.: 32 AF XY: 0.450 AC XY: 33385 AN XY: 74242

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.449

Alfa AF: 0.452 Hom.: 12758

Bravo AF: 0.447

Asia WGS AF: 0.406 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.50

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: rs2976392; hg19: chr8-143762932; COSMIC: COSV56652755;