rs2976391

chr8-142681306-C-Achr8-142681306-C-Gchr8-142681306-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]

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]

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	UniProt
PSCA	NM_005672.5	c.26-21C>A		intron_variant		ENST00000301258.5
PSCA	NR_033343.2	n.273-21C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSCA	ENST00000301258.5	c.26-21C>A		intron_variant		1	NM_005672.5	P1

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;