8-142679685-C-G

Variant names:

• chr8-142679685-C-G
• rs6471587
• ENST00000505305.1:n.262-1642C>G

Variant summary

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

The ENST00000505305.1(PSCA):​n.262-1642C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 152,240 control chromosomes in the GnomAD database, including 580 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 0.060 (580 hom., cov: 33)
• Consequence: PSCA ENST00000505305.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505305.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	NR_033343.2		n.273-1642C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSCA	ENST00000505305.1	TSL:3	n.262-1642C>G		intron	N/A
	PSCA	ENST00000510969.1	TSL:2	n.249-1642C>G		intron	N/A
	JRK	ENST00000587883.5	TSL:2	n.264+2020G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9139 AN: 152122 Hom.: 578 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0602 AC: 9161 AN: 152240 Hom.: 580 Cov.: 33 AF XY: 0.0591 AC XY: 4401 AN XY: 74444

African (AFR) AF: 0.156 AC: 6479 AN: 41520

American (AMR) AF: 0.0285 AC: 436 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.113 AC: 586 AN: 5176

South Asian (SAS) AF: 0.0513 AC: 247 AN: 4816

European-Finnish (FIN) AF: 0.0118 AC: 125 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1137 AN: 68028

Other (OTH) AF: 0.0548 AC: 116 AN: 2116

Alfa AF: 0.0403 Hom.: 49

Bravo AF: 0.0656

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs6471587; hg19: chr8-143761103;