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]

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=-0.92).
• 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	UniProt
PSCA	NM_005672.5	c.133+80G>A		intron_variant		ENST00000301258.5
PSCA	NR_033343.2	n.380+80G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSCA	ENST00000301258.5	c.133+80G>A		intron_variant		1	NM_005672.5	P1

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;