chr8-142670817-T-C

Position:

• chr8-142670817-T-C

Variant summary

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

The NR_033343.2(PSCA):​n.272+249T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,068 control chromosomes in the GnomAD database, including 12,944 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 0.41 (12944 hom., cov: 32)
• Consequence: PSCA NR_033343.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSCA	NR_033343.2	n.272+249T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSCA	ENST00000505305.1	n.261+249T>C		intron_variant, non_coding_transcript_variant		3
PSCA	ENST00000510969.1	n.248+249T>C		intron_variant, non_coding_transcript_variant		2
JRK	ENST00000591357.5	n.265-685A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62520 AN: 151952 Hom.: 12940 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.411 AC: 62543 AN: 152068 Hom.: 12944 Cov.: 32 AF XY: 0.408 AC XY: 30293 AN XY: 74334

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.421

Alfa AF: 0.343 Hom.: 2191

Bravo AF: 0.412

Asia WGS AF: 0.303 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9297976; hg19: chr8-143752235;