8-142679754-C-T

Variant names:

• chr8-142679754-C-T
• rs13262164
• ENST00000505305.1:n.262-1573C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000505305.1(PSCA):​n.262-1573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,142 control chromosomes in the GnomAD database, including 4,390 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 0.22 (4390 hom., cov: 33)
• Consequence: PSCA ENST00000505305.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSCA	NR_033343.2	n.273-1573C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSCA	ENST00000505305.1	n.262-1573C>T		intron_variant	Intron 1 of 1	3
PSCA	ENST00000510969.1	n.249-1573C>T		intron_variant	Intron 1 of 2	2
JRK	ENST00000587883.5	n.264+1951G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33976 AN: 152024 Hom.: 4380 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33996 AN: 152142 Hom.: 4390 Cov.: 33 AF XY: 0.227 AC XY: 16842 AN XY: 74356

African (AFR) AF: 0.108 AC: 4477 AN: 41536

American (AMR) AF: 0.319 AC: 4875 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3468

East Asian (EAS) AF: 0.147 AC: 757 AN: 5166

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4820

European-Finnish (FIN) AF: 0.319 AC: 3372 AN: 10568

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17801 AN: 67986

Other (OTH) AF: 0.227 AC: 480 AN: 2114

Alfa AF: 0.254 Hom.: 700

Bravo AF: 0.215

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.66
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs13262164; hg19: chr8-143761172;