rs2978974

Variant names:

• chr8-142670446-G-A
• rs2978974
• ENST00000505305.1:n.139G>A

Variant summary

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

The ENST00000510969.1(PSCA):​n.126G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,100 control chromosomes in the GnomAD database, including 11,275 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 0.38 (11265 hom., cov: 32)
  • Exomes 𝑓: 0.35 (10 hom.)
• Consequence: PSCA ENST00000510969.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NR_033343.2	n.150G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000505305.1	n.139G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3
PSCA	ENST00000510969.1	n.126G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
JRK	ENST00000591357.5	n.265-314C>T		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57157 AN: 151872 Hom.: 11250 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.345 AC: 38 AN: 110 Hom.: 10 Cov.: 0 AF XY: 0.375 AC XY: 30 AN XY: 80

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.376 AC: 57214 AN: 151990 Hom.: 11265 Cov.: 32 AF XY: 0.368 AC XY: 27327 AN XY: 74308

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.370

Alfa AF: 0.360 Hom.: 10765

Bravo AF: 0.383

Asia WGS AF: 0.287 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.50
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2978974; hg19: chr8-143751864;